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otto9otto says | |||
| There are many ways of maintaining, and increasing, human intelligence. Here are a few of the methods I am familiar with: 1. Aerobic exercise 2. Consuming a combination of uridine, choline, and fish oil. 3. Consuming acetyl L-carnitine arginate. 4. Playing "Dual N-Back". 5. Consuming gotu kola. 6. Consuming turmeric. 7. Consuming cannabis. I am interested in what other think of these, as well as other methods of cognitive enhancement. |
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| Total Topic Karma: 5 | - More by this Author | |||
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otto9otto says |
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| I forgot one more brain-healthy practice: calorie restriction. Curcumin, the active constituent of turmeric, is poorly absorbed. It is best consumed in the middle of a meal that contains fat. |
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| - Author's History - 11 May, 2009 | |||||
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Lewis says |
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| is any of this true, I doubt any game will lead to increased intelligence or smoking cannabis for that matter taking drugs enhances your perception of intelligence not your actual intelligence | |||||
| - Author's History - 22 August, 2009 | |||||
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gadget00 says |
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| Getting drugs actually cracks your neural system, so i don't think it really helps you actually | |||||
| - Author's History - 08 September, 2009 | |||||
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otto9otto says |
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| More on brain games. Just google the term "n-back". There are LOTS of free sites on the 'net to play this wonderfully beneficial game. I am personally up to getting an occasional perfect score on dual 5-back. More on aerobic exercise and neural plasticity. Also check out bacopa monieri, huperzine, rosemary, idebenone, avoid obesity, and minimize alcohol. Oh yeah: more on cannabis. |
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| - Author's History - 08 September, 2009 | |||||
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otto9otto says |
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| Supplements for Better Brain Power | |||||
| - Author's History - 13 November, 2009 | |||||
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otto9otto says |
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| Strawberries! | |||||
| - Author's History - 03 December, 2009 | |||||
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otto9otto says |
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CR (calorie restriction) maintains aging brain synaptic plasticity, seems to evidence the below paper, if three markers of the synaptic plasticity are valid. Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat. Djordjevic AM, Perovic M, Tesic V, Tanic N, Rakic L, Ruzdijic S, Kanazir S. Neurochem Int. 2009 Oct 27. [Epub ahead of print] PMID: 19878701 Abstract Brain aging is related to the numerous structural and functional changes including decreased synaptic plasticity. The beneficial effects of dietary restriction (DR) are well known but insufficiently investigated at the level of plasticity-related markers. Therefore, the aim of this study was to examine the expression profiles of proteins structurally and functionally related to synapses-growth-associated protein 43 (GAP-43), synaptophysin (SPH) and alpha-synuclein (alpha-Syn), in the course of aging and in response to long-term DR. The mRNA and protein levels of three presynaptic proteins were assessed by Real Time RT-PCR and Western blotting in the cortex and hippocampus of young (6-month-old), middle-aged (12-month-old), aged (18-month-old) and old (24-month-old) male Wistar rats fed ad libitum and exposed to DR starting from 6 months of age. We observed that long-term DR modulated age-related transcriptional changes by maintaining stable mRNAs levels in the cortex. No major age-related changes of the protein levels were observed in the cortex, while the specific temporal decline was detected in the hippocampus for all three proteins. The SPH levels were decreased across lifespan (0.8-, 0.8- and 0.6-fold change at 12, 18 and 24 months), while the significant decrease of GAP-43 and alpha-Syn protein was detected at 24 months of age (0.6- and 0.7-fold decrease, respectively). Long-term DR eliminated this decline by increasing GAP-43, SPH and alpha-Syn protein levels (1.7-, 1.7- and 1.6-fold, respectively) thus reverting protein levels to the values measured in 6-month-old animals. Specific pattern of changes observed in the hippocampus identifies this structure as more vulnerable to the processes of aging and with a more pronounced response to the DR effects. The observed DR-induced stabilization of the levels of three presynaptic proteins indicates the beneficial effect of DR on age-related decline in the capacity for synaptic plasticity. Keywords: GAP-43; Synaptophysin; alpha-Synuclein; Dietary restriction; Aging; Rat cortex; Hippocampus; Synaptic plasticity 1. Introduction There is growing evidence that physiological brain aging and age-related cognitive impairments are not accompanied by severe neuronal cell loss (Burke and Barnes, 2006). However, numerous changes in synaptic capacity undoubtedly occur with age. Aging is accompanied by structural and functional alterations that directly affect neural plasticity. Although, the adult brain retains a limited capacity for plastic reorganization/remodeling, age-associated synaptic dysfunction/reorganization takes place in many brain areas ([Cabeza et al., 1997], [Della-Maggiore et al., 2000] and [Grady et al., 2003]). This may be a reflection of the normal aging process, or it could be an attempt to overcome the decline in efficiency of existing functional networks through establishment of new ones (Grady et al., 1995). Of the environmental factors that can facilitate neuronal adaptability to the aging process, dietary restriction (DR) is the most promising, especially as DR can apparently prolong the lifespan, attenuate aging and prevent and/or delay the onset of numerous age-associated diseases (Cutler and Mattson, 2006). Deficits in learning and memory frequently associated with aging were prevented by DR ([Ingram et al., 1987] and [Means et al., 1993]). Direct beneficial effects of DR on synapses and improved synaptic defense to metabolic and oxidative damage were observed (Guo et al., 2000). Age-related changes in the turnover of synaptic membrane constituents can be affected by DR (Ando et al., 2002). In addition, of the genes whose transcriptional levels were changed under a restricted diet regimen, 25% were synaptic plasticity genes ([Prolla, 2002] and [Park and Prolla, 2005]). However, the impact of long-term caloric restriction on the expression of individual proteins that are structurally and/or functionally important for synaptic functioning has not been investigated. Growth-associated protein 43 (GAP-43) is a membrane-bound protein found in the growth cones and presynaptic terminals (Skene et al., 1986). It is implicated in different forms of synaptic plasticity, including neurite outgrowth, regeneration and long-term potentiation (LTP) (Benowitz and Routtenberg, 1997). The highest level of GAP-43 was observed during synaptogenesis, while its synthesis in the adult brain correlates with regenerative processes that take place in highly plastic brain areas ([Piehl et al., 1998], [Zhang et al., 2005] and [Simmons et al., 2008]). GAP-43 is an intrinsic determinant in the establishment and reorganization of synaptic connections (Hrdina et al., 199  and thus considered a marker of synapticplasticity. Synaptophysin (SPH) is one of the main integral proteins of synaptic vesicles. It is involved in vesicle trafficking, docking and fusion with the synaptic plasma membrane and neurotransmitter secretion ([Greengard et al., 1993] and [Iwamoto et al., 2004]), processes that are highly complex (Trikash et al., 200 . The developmental sequence of synaptophysinexpression can be correlated with the maturation of presynaptic terminals (Lou and Bixby, 1995). Changes in synaptophysin immune reactivity could reflect changes in the number of synaptic vesicles and have thus been used as a marker of synaptic density and as a marker of disordered synaptic connectivity in many brain diseases ([Masliah et al., 1991] and [Honer et al., 1999]). Together with GAP-43, SPH is highly expressed in adult brain regions with a potential for plastic changes. alpha-Synuclein (alpha-Syn) is a presynaptic protein involved in synaptic plasticity and neurodegeneration, processes highly influenced by aging. It is prominently expressed in the cortex and hippocampus, brain regions with a high synaptic plasticity potential (Maroteaux and Scheller, 1991). While aggregates of alpha-Syn are found in several neuropathological conditions known as synucleinopathies, its precise physiological role related to synaptic functioning and plasticity is still unknown. It has been postulated that alpha-Syn regulates the size of the presynaptic vesicular pool (Murphy et al., 2000), neurotransmitter release and processes associated with the organization and regulation of synaptic vesicles ([Kahle et al., 2000] and [Perez et al., 2002]). Thereby it plays a role in modulating synaptic functioning in the normal brain. Delayed developmental expression of alpha-Syn compared to synaptophysin, suggests its role in maintenance rather than formation of synapses ([Withers et al., 1997] and [Murphy et al., 2000]). Data on alpha-Syn expression during aging vary from marked decrease, to age-induced increase, and with no changes detected ([Petersen et al., 1999], [Stephan et al., 2002], [Li et al., 2004] and [Adamczyk et al., 2005]). In our previous report, we found a significant increase in alpha-Syn mRNA levels during aging in the rat cortex and hippocampus and its suppression by long-term DR (Mladenovic et al., 2007). In order to further investigate age-related changes in synaptic plasticity and elucidate the beneficial effects of lifelong DR, we examined the expression of three presynaptic proteins: synaptophysin, GAP-43 and alpha-Syn in the brain cortex and hippocampus of young (6-month-old), middle-aged (12-month-old), aged (18-month-old) and old animals (24-month-old). 2. Materials and methods 2.1. Animals and treatments Male Wistar rats were used ... with food available ad libitum (AL) until 6 months of age (young) when they were divided into two groups. Group AL continued to receive food ad libitum; the group subjected to dietary restriction (DR group) was allowed 50% of the mean daily intake of the AL group every 2nd day. The rats (N = 6 per group) were maintained on this dietary regime up to 12 (middle-aged), 18-(aged) and 24-(old)-months of age. Following monthly checks in food consumption and constant monitoring of animal body weight, health and activity, the amounts of daily intake in the AL and DR groups were adjusted according to the calculated values. ... Under this dietary regimen, as previously shown (Perovic et al., 2009), a continual increase of the mean body weight was observed in the AL group up to 18 months of age that was followed by a decrease observed in 24-month-old rats, while under DR treatment, the mean body weight of animals remained similar across all ages and at no time exceeded the mean body weight of the AL group. In addition, in the DR group 3-fold more animals reached the age of 24 months. ... ... 3. Results In order to determine the patterns of change of three presynaptic proteins: growth-associated protein 43 (GAP-43), synaptophysin (SPH) and alpha-synuclein (alpha-Syn) in the cortex and hippocampus during aging and to examine the effect of long-term dietary restriction, we assessed mRNA levels by Real Time RT-PCR and protein levels by Western blot analysis. 3.1. Effect of age and DR on the level of mRNAs Age induced changes in GAP-43 mRNA levels in both the cortex and hippocampus (Fig. 1a and b, white bars). In the cortex, a 1.5-fold increase was observed at 24 months of age, while in the hippocampus elevated mRNA levels were detected during the entire aging period, i.e. 1.5-, 1.4- and 1.3-fold increases were observed in 12-, 18- and 24-month-old rats, respectively. Conversely, after the initial decrease (0.7-fold) in the cortex of 12-month-old animals, the SPH mRNA level returned to the control value and steady-state levels of mRNA were maintained during the entire aging period (Fig. 1c, white bars). No age-related changes in SPH mRNA expression were observed in the hippocampus (Fig. 1d, white bars). Following exposure to long-term DR, attenuation of age-induced changes in GAP-43 mRNA levels were detected in the cortex (Fig. 1a, grey bars). DR induced reduction of GAP-43 mRNA level by 0.5-fold compared to the age-matched control, thus lessening the age-induced increase observed in 24-month-old animals. However, while the observed age-associated increase of GAP-43 mRNA level in the cortex of the oldest animals was influenced by DR, no such effect was detected in the hippocampus where the DR-related decrease was below statistical significance (Fig. 1b, grey bars). The age-induced decline in SPH mRNA observed in the cortex of 12-month-old rats was attenuated by a DR-induced 1.2-fold increase in mRNA (Fig. 1c, grey bars). No effects of long-term DR were observed for SPH mRNA levels in the hippocampus (Fig. 1d, grey bars). 3.2. Effect of age and DR on the level of proteins Aging did not induce major changes in the level of examined proteins in the cortex except for a slight but significant (0.8-fold) decrease of SPH protein in 24-month-old animals (Fig. 2a, c and e, white bars). However, in the hippocampus an age-related decrease of all three presynaptic markers was observed (Fig. 2b, d and f, white bars). A decline in GAP-43 and alpha-Syn levels was observed during aging, although it was statistically significant only in the oldest rats (0.6- and 0.7-fold decreases of GAP-43 and alpha-Syn, respectively). Decreased SPH protein level was detected as early as 12 months of age (0.8-fold). It remained below the control level during the entire aging period and reached about 60% (a 0.6-fold change) of the control level at 24 months of age. Analysis of the effects of long-term DR revealed significant changes at the protein level that were more prominent in the hippocampus than in the cortex (Fig. 2, grey bars). A statistically significant 0.7-fold decrease of GAP-43 level was observed under the influence of DR in 24-month-old rats, whereas a 1.3-fold increase in alpha-Syn protein level was measured in the cortex of 18-month-old rats (Fig. 2a and e, grey bars). In the hippocampus, DR induced the most prominent changes in levels of all three proteins (Fig. 2b, d and f, grey bars). The level of SPH gradually increased under DR, starting from 18 months (1.2-fold) and up to 24 months of age (1.7-fold), with respect to age-matched counterparts. At 24 months of age, the time point of the longest exposure to DR, significant increases in GAP-43 and alpha-Syn levels were also observed (1.7- and 1.6-fold, respectively). Compared to the effect of aging, DR reverted the levels of all three proteins to those measured in young, 6-month-old animals (1.1-, 1- and 1.2-fold for GAP-43, SPH and alpha-Syn, respectively). 4. Discussion In this study, we assessed the effects of aging and lifelong dietary restriction on neuroplasticity by examining the expression pattern of three important presynaptic proteins in the cortex and hippocampus, brain structures that are very susceptible to the aging process. We evaluated the levels of neuronal growth-associated protein GAP-43, the marker of nerve cell structural adaptive capabilities, synaptophysin, the marker of the fate of presynaptic terminals and alpha-Syn, the marker of reserve synaptic vesicle pool functionality. Aging affected the expression of GAP-43, SPH, alpha-Syn in a region-specific manner and lifelong dietary restriction counteracted the age-related changes in their expression, observed as the almost complete restoration of their respective mRNA levels in the cortex and protein levels in the hippocampus. Previously, we showed an age-related increase in alpha-Syn mRNA (Mladenovic et al., 2007) in the hippocampus and cortex. In this study we presented evidence for similar temporal and regional patterns of GAP-43 mRNA changes while the SPH mRNA profile remained mostly unchanged during aging in both structures. Relatively stable levels of all three proteins were found in the cortex and hippocampus except in very old, 24-month-old animals. This age is characterized by a major decline of all three proteins in the hippocampus. Our data are consistent with previous reports that described a general trend of reduction of synaptic proteins in the hippocampus, compared to younger counterparts (Adams et al., 200 . It should be noted that other authors didnot detect such changes ([Willcox and Scott, 2004] and [Eastwood et al., 2006]) and that some even reported increases in GAP-43 and SPH mRNA and protein levels during aging ([Himeda et al., 2005] and [Benice et al., 2006]). Contradictory results also exist for alpha-Syn mRNA and protein levels ([Petersen et al., 1999], [Adamczyk et al., 2005] and [Malatynska et al., 2006]). Nevertheless, the reported age-induced increase in mRNA levels ([Stephan et al., 2002] and [Mladenovic et al., 2007]) could represent a compensatory mechanism for the age-related depletion of soluble alpha-Syn protein that we and others have observed ([Wang et al., 2004] and [Adamczyk et al., 2005]). These controversies could be attributed to the different sensitivities of the methods used, in addition to different brain regions, animal strains and sexual differences. Also, in our study, unlike in most other published studies in which only young animals were compared with old animals, changes across the entire lifespan were assessed, including middle age which represents a critical point that is useful for detecting events leading to senescence. By examining four time points, in addition to regional specificities, we were also able to demonstrate the specificities of age-related kinetics for presynaptic proteins. Brain areas differ greatly in their vulnerability to aging. Studies investigating the impact of age on the cortex and hippocampus found these structures especially vulnerable to aging (Uylings and de Brabander, 2002) and various pathological conditions ([Mateos et al., 2008] and [Taneichi-Kuroda et al., 2009]). The different pattern of changes in the cortex and hippocampus that we described here revealed that the hippocampus was very susceptible to aging. The observed decline of GAP-43 in 24-month-old rats could reflect the age-related decrease in the structural adaptive capabilities of nerve cells and of the reduction of axon plasticity in the hippocampus. Additionally, the significant reduction in hippocampal SPH and alpha-Syn protein levels point to a synaptic deterioration with aging. Alterations in SPH are not necessarily coupled with changes in the number of synapses but may reflect variations in the number of presynaptic vesicles and their size. Quantitative ultrastructural analysis of synapses did not show age-related changes in synapse number in specific areas of the hippocampus (Shi et al., 2007). Thus, decreased SPH protein levels in the cortex and hippocampus during aging probably result from a continuous decline in synaptic functionality rather than the loss of synapses. Nevertheless, decreased expression of all the three presynaptic proteins in the hippocampus of 24-month-old rats supports the concept that synapses and/or their components become increasingly vulnerable during aging (Bennett et al., 2006) and that disruptions of synaptic architecture and functioning occur. In addition to the regional specificities during aging, specific temporal patterns of decline were observed for the three presynaptic proteins, suggesting that certain compensatory synaptic changes occur during aging. Here we observed a continual decrease of SPH protein levels in the hippocampus while the levels of GAP-43 and alpha-Syn remained unchanged throughout senescence, except in the oldest animals. The situation where SPH loss precedes loss of GAP-43 is present in some neurodegenerative disorders such as Alzheimer's disease where, despite synapse loss that occurs very early, certain compensatory mechanisms are still in place through upregulation of GAP-43 (Masliah et al., 2001). Any process that involves axonal membrane remodeling such as neurite growth, is expected to have upregulated GAP-43 expression. If we take the ratio of GAP-43 to SPH to represent the index of newly formed synapses, then during aging in both the cortex and hippocampus, functionality was lost before the disappearance of synapses. The effects of dietary restriction on neuroplasticity and neuroprotection were observed in numerous clinical and epidemiological studies (for a review see Mattson et al., 2002). The impact of DR on age-associated alterations in gene expression is highly dependent on the class of gene and brain regions under examination ([Prolla, 2002] and [Park and Prolla, 2005]). Although DR was found to induce transcriptional reprogramming of neural plasticity genes, limited or no data is available for the three presynaptic proteins that were examined in our study. The present study shows that long-term DR can modulate age-related transcriptional changes of two presynaptic markers, GAP-43 and SPH. In our previous study, we showed that DR counteracted the age-related increase of alpha-Syn mRNA in the cortex and hippocampus, the effect being more prominent in old rats (Mladenovic et al., 2007). Here we show that age-related changes in GAP-43 and SPH mRNA levels were completely or partially prevented by DR in the cortex, while the effect of DR in the hippocampus was not mediated by modulation of age-induced changes in mRNA levels but by the maintenance of stable levels across the entire lifespan. However, in the hippocampus lifelong dietary modulation increased the levels of the three proteins whose expression significantly decreases during aging. The DR-induced expression profiles of mRNAs and proteins did not correlate both in the hippocampus and cortex. This discrepancy which has been observed for an increasing number of proteins, including some synaptic proteins ([Petersen et al., 1999] and [Eastwood et al., 2006]), suggests that the DR-induced increase in GAP-43, SPH and alpha-Syn was not due to increased transcription or mRNA stability but rather to enhanced translation and/or increased protein stability. While to our knowledge there is no available data that describes the effect of DR on GAP-43 and alpha-Syn expression, various dietary regimes have been shown to affect SPH levels. The age-related decrease in the turnover rate of SPH was found to be accelerated by dietary restriction (Ando et al., 2002). Similar to our results, Adams et al. (200 found a significant increase ofSPH in old animals that had been subjected to DR compared to AL controls. The increased levels of all three presynaptic proteins observed in the aged hippocampus indicate synaptic changes following DR. Also, the finding that DR differentially affected SPH expression compared to GAP-43 and alpha-Syn, points to ongoing synaptic remodeling. Since changes in the number of synapses were not found following DR in the rat hippocampus (Shi et al., 2007), the elevated levels of all three presynaptic proteins could be a reflection of the changes in synaptic function and/or structure. The beneficial effect of DR-promoted amelioration of age-related changes has been shown for other proteins associated with synaptic plasticity in the hippocampus ([Prolla, 2002], [Park and Prolla, 2005] and [Adams et al., 2008]). Elevated GAP-43 and alpha-Syn protein levels, in addition to SPH, suggest that a presynaptic compensatory mechanism is activated in the hippocampus during lifelong DR. In summary, our data demonstrated specific pattern of changes in the hippocampus where the progressive age-related decline in the level of three presynaptic proteins could be prevented by long-term DR. In the cortex DR attenuated the age-induced changes at the mRNA level. Thus, the beneficial effect of DR on promoting neuronal plasticity could be in part mediated by the stabilization of SPH, GAP-43 and alpha-Syn levels through the lifespan. |
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| - Author's History - 08 December, 2009 | |||||
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otto9otto says |
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| Still more on aerobic exercise! For this reason, I sweat "mouse sweat" at the gym every other day! | |||||
| - Author's History - 23 January, 2010 | |||||
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otto9otto says |
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| Amitriptyline. Now if I can only get some progressive physician to prescribe it for me... | |||||
| - Author's History - 26 January, 2010 | |||||
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otto9otto says |
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| Magnesium and sleep. | |||||
| - Author's History - 28 January, 2010 | |||||
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otto9otto says |
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| Carnosine The best (cheapest) source I have found is Bulk Nutrition |
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| - Author's History - 01 February, 2010 | |||||
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otto9otto says |
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| Hesperidin , part of the complex of citrus bioflavinoids, present in most such supplements even if it is not specifically assayed, such as this one . Also the Mediterranean Diet. |
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| - Author's History - 09 February, 2010 | |||||
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otto9otto says |
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| More evidence that n-back type games increase intelligence . There is plenty of places on the web to play this for free. Just google "n-back". | |||||
| - Author's History - 23 February, 2010 | |||||
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otto9otto says |
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| Inflammation. This article suggests an expensive supplement, but there are lots of ways to reduce chronic inflammation, including simply losing excess weight. Just google the term. Grape seed extract. I get this stuff cheaply from bulk nutrition. |
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| - Author's History - 01 March, 2010 | |||||
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Mad Ant says |
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| I've read that Creatine, which is generally considered an exercise food supplement, also helps for cognitive abilities. | |||||
| - Author's History - 21 March, 2010 | |||||
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otto9otto says |
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Central Nervous System Agents in Medicinal Chemistry, 2007, 7, 109-114 109 1871-5249/07 $50.00+.00 ? 2007 Bentham Science Publishers Ltd. Brain Senescence and Neuroprotective Dietary Components Keiko Unno and Minoru Hoshino Abstract: Senescence is an ageing process characterized by progressive and irreversible dysfunction of various physiological systems. Physiological senescence with advancing age is not a disease, but it affects the life-span and life-quality of elderly people. Brain functions such as cognition and motor skills, as with other organ systems, are impaired in almost all elderly people. Neuroprotective dietary components can play a key role in ensuring healthy ageing of the brain. Although the causative mechanisms of senescence are complex and not yet fully elucidated, enhanced oxidative stress is thought to be an important contributor. Dietary antioxidants from fruits and vegetables have preventative effects on oxidative stress. Catechin, a polyphenol found in green tea, has a potent antioxidative effect. Recently, catechin has been reported to protect against reduced ageing-related cognitive functions such as those associated with learning and memory, and ischemic brain damage. Catechin may act as a neuroprotective agent in progressive neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. The neuroprotective effects and putative mechanisms of action of catechin and other antioxidants are examined and discussed in this review. Keywords: Antioxidant, brain, green tea catechin, learning & memory, oxidative damage, senescence. INTRODUCTION The proportion of elderly people in the population is increasing in many countries. Ageing is an important risk factor for diseases such as cancer, cardiovascular-related disorders, diabetes and dementia. Furthermore, almost all elderly people show brain atrophy and cognitive dysfunction, even if they exhibit no distinct pathology. Since the maximum longevity and number of cell divisions are fixed in each organism, the process of ageing is, to a large degree, programmed. However, the level of brain regression among age-matched people varies, suggesting that brain senescence may be prevented or delayed by improvements or alterations in lifestyle. Although the factors and mechanisms underlying senescence and neurodegenerative disease involved are complex, and include both genetic and environmental factors, enhanced oxidative stress has been proposed to play a major role in both processes [for example, see 1-4]. The brain is highly susceptible to oxidative damage because it consumes a large amount of oxygen and generates an abundance of free radicals as normal products of cellular metabolism [5-7]. In aged organisms, the defense response against reactive oxygen species associated with oxidative damage may decline or become defective. Oxidative damage is thought to be a cause of age-related decline in learning and memory [8]. In addition, several conditions involving age-related brain dysfunction, such as Alzheimer's (AD) and Parkinson's disease (PD), involve oxidative damage. Thus, prevention of oxidative damage to the brain is likely to be beneficial for the maintenance of cognitive function. Neuroprotective dietary components have an essential role in facilitating healthy ageing of the brain [9, 10]. Dietary antioxidants from fruits and vegetables have preventative effects on oxidative stress [11-16]. Green tea catechin (GTcatechin) is a mixture of plant polyphenols that have potent antioxidative and radical-scavenging activities [17-21]. In this respect, it is important to determine whether antioxidants derived from nutritional sources have preventive and/or therapeutic effects on declining learning and memory functions and neurodegenerative disorders. The effect of dietary supplements may occur directly in the brain. To understand the neuroprotective function of dietary antioxidants, we focused on the properties of GT-catechin, including its antioxidative and radical scavenging activities, distribution and metabolism, and alterations in brain senescence and neurodegenerative state. In addition, other dietary components that may be effective for altering brain senescence are described. 1. GREEN TEA CATECHINS GT-catechin, a polyphenol, is the main component of green tea, and has a bitter and astringent taste. In Japanese green tea, the average content is about 10-20%, although this varies with season, location and growing condition. When green tea (5-10 g) is extracted with 100 ml of hot water, the content of catechins is about 60 mg, or ~30-40% of the dried extract. GT catechin consists mainly of (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG) and (-)-epicatechin (EC; Fig. 1). The catechin content of black tea is lower, ranging from 3-10%, but it has a higher content of theaflavins and other polyphenols. 1.1. Antioxidative and Radical Scavenging Activities GT-catechin has strong antioxidative and radical scavenging activities. Such activity is dependent on the position (o-, m-, p-) of the diphenol hydroxyl group. The compounds that have neighboring hydroxyl groups have higher antioxidative activity. When measured using an oxygen electrode [22], the antioxidative activity of EGCG is higher than those of other GT-catechins (EGCG>ECG??EGC>>EC), with the activity being dependent on the number of hydroxyl groups in the compound. Green tea solutions have antioxidative activity comparable to, or higher than, that of EGCG. The antioxidative activities of GT-catechin are affected by pH and metal ions. GT-catechin has peak activity at pH 6-12. Cu2+ and Mn2+ increased the antioxidative activity of EGCG, whilst Fe2+ has an inhibitory effect [23]. Iron preferentially binds to the gallate group of EGCG and ECG, with binding destabilizing the formation of the phenoxyl radical formed from the hydroxyl group in the gallo-catechin of EGCG and EGC. The scavenging rates of GT-catechin are altered by free radicals in a complex reaction. For example, the reaction rates (M-1s-1) of GT-catechins are in the order of 109 with hydroxyl radical, 105 with superoxide anion, and 103 with 1,1-diphenyl-2-picrylhydrazyl (DPPH), respectively [24]. The reaction rate of EGCG with hydroxyl radical is 7 times higher than that of EC. One molecule of EGCG scavenges 14 molecules of DPPH [25]. When scavenging activity (1 g of dry weight eluted from water and dimethyl sulfoxide) is compared using a fluorescent probe and superoxide anion generator, the activity of green tea against DPPH is ~20-fold higher, and the activity against superoxide anion (O2-) ~20- 30 times higher than those of blueberry and strawberry [26]. 1.2. Distribution and Metabolism EGCG administered orally is rapidly absorbed, and is distributed mainly into the liver, plasma and mucous membranes of the small intestine [27]. EGCG distributed in plasma has been calculated to be ~2% of consumed EGCG. Using chemiluminescence-detection HPLC, after 1 h administration, the level of EGCG in brain is detectable at a low level [27]. Using [3H]-EGCG dosing in mice, after a 6 h interval, a second equal administration enhances the level of radioactivity in blood, brain, liver (and in several other tissues), at 4-6 times above those after a single administration [28]. This suggests that frequent consumption of green tea enables the body to maintain a high-level of GT-catechin. Another study of metabolic fate in rats using [4-3H] EGCG found that radioactivity peaked at 24 h in blood, brain and other tissues, with EGCG degradation products being conjugated with glucuronide in the intestine [29]. Therefore, while the level of GT-catechin in the brain may low after the initial administration of green tea, multiple administrations may increase these levels. Furthermore, the distribution of GTcatechin metabolites may be an important indicator of antioxidant activity. The glucuronide conjugates exhibit high antioxidative activity [30, 31]. Measurement of the antioxidative and physiological activity of other metabolites, such as those conjugated to sulfate, or methylated or hydrated may be a useful index of such activity. Further detailed analysis of the distribution of EGCG and its metabolites in brain would be helpful to clarify the potential neural effects of GT-catechin and its metabolites. 2. IMPROVEMENT OF BRAIN ATROPHY AND FUNCTION BY GT-CATECHIN To investigate the complex mechanisms underlying brain senescence, a suitable animal model is required. We investigated the influence of GT-catechin intake on brain function, cerebral atrophy and oxidative damage in mice with accelerated senescence (SAMP10). SAMP10 is a useful mouse model of brain senescence, as such mice are an inbred strain having cerebral atrophy and decreased memory and learning abilities, due to neuronal loss in later life [32-34]. 2.1. Cerebral Atrophy in Aged SAMP10 Mice Experimental mice had free access to a normal diet (CE- 2; Clea Co Ltd, Tokyo, Japan) and tap water containing 0.02% GT-catechin (Polyphenon 70S, Mitsui Norin Co Ltd, Tokyo, Japan) from the age of 1 month. Polyphenon 70S contains above 70% GT-catechin analyzed as below. The GT-catechin consists of 31.7% EGCG, 15.7% EGC, 10.0% ECG, 8.5% EC, 4.5% (-)-gallocatechin gallate, and 1.0% (-)- catechin gallate. The remaining portion consists of other catechins from green tea and no caffeine. Each mouse consumed 5-15 ml of 0.02% catechin water per day. The mean dose of GT-catechin was calculated to be ~35 mg/day/kg. The mean body weight of mice fed catechin water was not significantly different from age-matched controls. However, the cerebral weight of 12-month-old control mice was significantly lower than that of those at 6 months. Interestingly, the cerebral atrophy was significantly suppressed in 12- month-old mice that had been fed GT-catechin water [35]. 2.2 Memory Acquisition and Retention Test We also tested the effects of GT-catechin on memory acquisition and retention using a step-through passiveavoidance task on SAMP10 mice. When a mouse entered a dark chamber from an illuminated one, the door was closed and an electric foot shock delivered at 0.5 mA for 1 s. Acquisition of the avoidance response was judged successful if the mouse remained in the illuminated chamber for 300 s. The trial was repeated until the mouse satisfied the acquisi- Otion criterion within five trials. The time required for learning in 11-month-old control SAMP10 mice was significantly longer than that for younger animals. However, the learning time significantly improved in 11-month-old SAMP10 mice that had received GT-catechin water [35]. One month later, mice were further examined to see whether they would remain in the illuminated chamber for 300 s. Many of the 6-month-old mice succeeded in remembering the avoidance response, although some of the 12- and 15-month-old mice entered the dark chamber. Aged mice that had been fed GT-catechin had a significantly lower failure ratio compared to age-matched controls (Fig. 2) [36]. Thus, memory was better maintained in the aged SAMP10 mice given catechin water. In humans, epidemiological studies show that a higher consumption of green tea is associated with a reduced prevalence of cognitive impairment [37]. In contrast, a weak or null relation between consumption of black or oolong tea or coffee and cognitive impairment has been described. These results from mice and human studies suggest that a higher consumption of green tea may attenuate brain senescence. 2.3. Oxidative Damage and Endogenous Antioxidative Activity The level of oxidative damage in aged brain associated with suppression of brain senescence by consumption of GTcatechin was investigated in SAMP10 mice. Oxidative damage to DNA was quantitated by measuring levels of the marker 8-oxodoxyguanosine in the cerebrum. There was significantly more oxidative damage in 15-month-old mice than 2-month-old mice [36]. However, in age-matched SAMP10 mice fed GT-catechin water, the level of oxidative damage to DNA was suppressed. In addition, the level of serum antioxidant activity in SAMP10 mice was also reduced with ageing, being significantly lower in 15-monthold SAMP10 mice than in 2-month-old SAMP10 mice [36]. The levels in aged mice fed GT-catechin were significantly higher than controls. Various antioxidants in blood plasma, such as ascorbic acid, albumin, bilirubin, and uric acid, are supplied via the circulation to tissues, where they suppress oxidative damage. GT-catechin in plasma might be preferentially metabolized over other antioxidants, resulting in increased antioxidative activity, as was found in the serum of the mice fed GT-catechin. In humans, continuous intake of GT-catechin has been reported to increase plasma antioxidant activity [38]. To evaluate the cerebro-protective effect of GT-catechin in ischemia, 0.5% GT-catechin was given to rats in drinking water from 5 days prior to transient middle cerebral artery occlusion [39]. GT-catechin reduced the brain infarct area and volume, inducible nitric oxide synthase expression, infiltration of neutrophils and formation of peroxynitrite. This effect of GT-catechin was postulated to occur via the scavenging properties of oxygen radicals and inhibition of nuclear factors that are regulated by the intracellular redoxstate. In aged rats in which oxidative stress was induced by chronic ethanol consumption, administration of GT-catechin protected lipid and proteins against oxidative modifications in the brain [40]. They showed that GT-catechin prevented changes in antioxidant enzymes and ethanol-induced antioxidant products, which were enhanced with ageing. In brain, GT-catechin (2 mg/kg) induced the activity of superoxide dismutase (SOD) and catalase [41]. The decreased activity of glutathion peroxidase was improved in cerebral cortex of aged SAMP10 mice fed GT-catechin water [42]. Furthermore, the neuroprotective activity of EGCG may directly exert its effects as a free radical scavenger in neurons, although EGCG significantly inhibited NF-kappa B activation in T cells [43]. These data suggest that antioxidative Fig. (2). GT-catechin consumption improves memory regression in aged mice. GT-catechin consumption represents mean + SEM (n = 15-23). Asterisk (*) and sharp (#) represent significant difference between young control and age-matched control, respectively (P |
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| - Author's History - 12 April, 2010 | |||||
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otto9otto says |
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| Green tea benefits | |||||
| - Author's History - 14 April, 2010 | |||||
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otto9otto says |
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| Mindfulness Meditation | |||||
| - Author's History - 17 April, 2010 | |||||
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Emily says |
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| Well, this isn't for everybody, but LSD. I did a lot last year and now I just have this expansive need to pursue knowledge, I stopped having memory problems, and I stopped caring about things like Family Guy and SNL and general wastes of times. I spend that time studying history or writing. Less serious things that I've found help a lot with concentration and memory is getting enough sleep, keeping fit, and meditation. | |||||
| - Author's History - 01 June, 2010 | |||||
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otto9otto says |
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| Effects of aging and calorie restriction on white matter in rhesus macaques. Bendlin BB, Canu E, Willette A, Kastman EK, McLaren DG, Kosmatka KJ, Xu G, Field AS, Colman RJ, Coe CL, Weindruch RH, Alexander AL, Johnson SC. Neurobiol Aging. 2010 Jun 10. [Epub ahead of print] PMID: 20541839 Abstract Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of caloric restriction likely include reductions in age-related inflammation and oxidative damage. Oligodendrocytes are particularly susceptible to inflammation and oxidative stress, therefore, we hypothesized that CR would have a beneficial effect on brain white matter and would attenuate age-related decline in this tissue. CR monkeys and controls underwent diffusion tensor imaging (DTI). A beneficial effect of CR indexed by DTI was observed in superior longitudinal fasciculus, fronto-occipital fasciculus, external capsule, and brainstem. Aging effects were observed in several regions, although CR appeared to attenuate age-related alterations in superior longitudinal fasciculus, frontal white matter, external capsule, right parahippocampal white matter, and dorsal occipital bundle. The results, however, were regionally specific and also suggested that CR is not salutary across all white matter. |
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| - Author's History - 18 June, 2010 | |||||
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otto9otto says |
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| Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24; 13 males, 11 females) and standard diets (n = 17; 8 males, 9 females). Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A diet x age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species. | |||||
| - Author's History - 20 June, 2010 | |||||
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editor says |
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| Check out Dakim | |||||
| - Author's History - 30 June, 2010 | |||||
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otto9otto says |
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| Piano Lessons Cyprenil/Deprenyl/Selegiline Calories may do brains harm before weight gain occurs: Journal club Nicola Clayton Nature Volume: 465, Page: 989 Date published: (24 June 2010) A comparative cognitive scientist considers the effects of high-calorie diets on the brain. It is well established that an excessive intake of high-calorie foods, unless coupled with plenty of exercise, leads to obesity, which is a growing public-health concern. As a dancer and a scientist, I am well aware of the intimate connection between the body and the brain, and not at all surprised by the recent accumulation of evidence showing that a high-calorie diet leads to a suite of cognitive impairments, particularly in memory. What is striking, however, is how quickly the effects can occur and how selective they are. Scott Kanoski and Terry Davidson at Purdue University in West Lafayette, Indiana, studied the effects of a high-energy diet on the memory performance of rats trained in a radial-arm maze (S. E. Kanoski and T. L. Davidson J. Exp. Psychol. Anim. Behav. Proc. 36, 313-319; 2010). They found that maintaining rats on a high-energy diet for just 72 hours was sufficient to result in a marked impairment in spatial memory. Deficits in non-spatial memory took much longer to detect, emerging only after 30 days. Spatial skills are therefore particularly vulnerable. This finding has important implications for our own lifestyle. Clearly, consuming an excessively high-calorie diet can result in marked decreases in cognitive abilities, especially in spatial memory. The fact that this occurs in such a short space of time, prior to any significant gain in body weight, suggests that diet-induced cognitive impairments could contribute to, rather than simply be a consequence of, obesity. So hide the high-calorie foods - if out of sight is out of mind, it might just save your brain! |
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| - Author's History - 06 July, 2010 | |||||
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otto9otto says |
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| Avoid methionine: see here and here. Methionine content of foods can be found here, here, and here. |
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| - Author's History - 07 July, 2010 | |||||
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otto9otto says |
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| The same molecular mechanism that increases life span through calorie restriction may help boost memory and brainpower, researchers at MIT's Picower Institute for Learning and Memory report in the July 11 issue of Nature. Resveratrol, found in wine, has been touted as a life-span enhancer because it activates a group of enzymes known as sirtuins, which have gained fame in recent years for their ability to slow the aging process. Now MIT researchers report that Sirtuin1 ? a protein that in humans is encoded by the SIRT1 gene ? also promotes memory and brain flexibility. The work may lead to new drugs for Alzheimer's disease and other debilitating neurological diseases. "We demonstrated previously that Sirtuin1 promotes neuronal survival in age-dependent neurodegenerative disorders. In our cell and mouse models for Alzheimer's disease, SIRT1 promoted neuronal survival, reduced neurodegeneration and prevented learning impairment," said Li-Huei Tsai, director of the Picower Institute and lead author of the study. "We have now found that SIRT1 activity also promotes plasticity and memory," said Tsai, Picower Professor of Neuroscience and a Howard Hughes Medical Institute investigator. "This result demonstrates a multi-faceted role of SIRT1 in the brain, further highlighting its potential as a target for the treatment of neurodegeneration and conditions with impaired cognition, with implications for a wider range of central nervous system disorders." In separate work at MIT, researchers discovered that the sir2 (silent information regulator) gene is a key regulator of longevity in both yeast and worms. Ongoing studies are exploring whether this highly conserved gene also governs longevity in mammals. The mammalian version of the gene, SIRT1, seems to have evolved complex systemic roles in cardiac function, DNA repair and genomic stability. SIRT1 is thought to be a key regulator of an evolutionarily conserved pathway that allows organisms to cope with adversity. These genes and the enzymes they produce are part of a feedback system that enhances cell survival during times of stress, especially a lack of food. Recent studies linked SIRT1 to normal brain physiology and neurological disorders. However, it was unknown if SIRT1 played a role in higher-order brain functions. The Picower Institute study shows that SIRT1 enhances synaptic plasticity, the connections among neurons, and memory formation. These findings demonstrate a new role for SIRT1 in cognition and a previously unknown mechanism by which SIRT1 regulates these processes. MicroRNAs are small RNA molecules encoded in the genomes of plants and animals. These gene regulators are involved in many aspects of normal and abnormal brain function. The Picower study found that SIRT1 aids memory and synaptic plasticity through a previously unknown microRNA-based mechanism: SIRT1 keeps a specific microRNA in check, allowing key plasticity proteins to be expressed. In addition to helping neurons survive, SIRT1 also has a direct role in regulating normal brain function, demonstrating its value as a potential therapeutic target for the treatment of the central nervous system. I get my resveratrol from BeyondACentury. Resveratrol absorbtion is enhanced by grapefruit juice and lecithin. |
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| - Author's History - 12 July, 2010 | |||||
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otto9otto says |
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| Be sagacious with sage. | |||||
| - Author's History - 24 July, 2010 | |||||
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