Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003.—One of the most significant challenges in neuroscience is to identify the cellular and molecu...

/pdf/long-term-potentiation-and-memory-3o23qnxlkq.pdf

Long-Term Potentiation and Memory

Distribution, interconversion, and dose response of n−3 fatty acids in humans

Background Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies, but there is limited study of whether this type of fat protects against Alzheimer disease. Objective To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease. Design Prospective study conducted from 1993 through 2000, of a stratified random sample from a geographically defined community. Participants were followed up for an average of 3.9 years for the development of Alzheimer disease. Patients A total of 815 residents, aged 65 to 94 years, who were initially unaffected by Alzheimer disease and completed a dietary questionnaire on average 2.3 years before clinical evaluation of incident disease. Main Outcome Measure Incident Alzheimer disease diagnosed in a structured neurologic examination by means of standardized criteria. Results A total of 131 sample participants developed Alzheimer disease. Participants who consumed fish once per week or more had 60% less risk of Alzheimer disease compared with those who rarely or never ate fish (relative risk, 0.4; 95% confidence interval, 0.2-0.9) in a model adjusted for age and other risk factors. Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease, as was intake of docosahexaenoic acid (22:6n-3). Eicosapentaenoic acid (20:5n-3) was not associated with Alzheimer disease. The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions. Conclusion Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease.

/pdf/consumption-of-fish-and-n-3-fatty-acids-and-risk-of-incident-4kuydyj1wq.pdf

Consumption of Fish and n-3 Fatty Acids and Risk of Incident Alzheimer Disease

Lipidomics, after genomics and proteomics, is a newly and rapidly expanding research field that studies cellular lipidomes and the organizational hierarchy of lipid and protein constituents mediating life processes. Lipidomics is greatly facilitated by recent advances in, and novel applications of, electrospray ionization mass spectrometry (ESI/MS). In this review, we will focus on the advances in ESI/MS, which have facilitated the development of shotgun lipidomics and the utility of intrasource separation as an enabling strategy for utilization of 2D mass spectrometry in shotgun lipidomics of biological samples. The principles and experimental details of the intrasource separation approach will be extensively discussed. Other ESI/MS approaches towards the quantitative analyses of global cellular lipidomes directly from crude lipid extracts of biological samples will also be reviewed and compared. Multiple examples of lipidomic analyses from crude lipid extracts employing these approaches will be given to show the power of ESI/MS techniques in lipidomics. Currently, modern society is plagued by the sequelae of lipid-related diseases. It is our hope that the integration of these advances in multiple disciplines will catalyze the development of lipidomics, and such development will lead to improvements in diagnostics and therapeutics, which will ultimately result in the extended longevity and an improved quality of life for humankind.

Shotgun lipidomics: Electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples

It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness.

/pdf/brain-foods-the-effects-of-nutrients-on-brain-function-2cng8bwpxq.pdf

Brain foods: the effects of nutrients on brain function

Docosahexaenoic acid (DHA), an n-3 fatty acid, is rapidly deposited during the period of rapid brain development. The influence of n-3 fatty acid deficiency on learning performance in adult rats over two generations was investigated. Rats were fed either an n-3 fatty acid-adequate (n-3 Adq) or -deficient (n-3 Def) diet for three generations (F1-F3). Levels of total brain n-3 fatty acids were reduced in the n-3 Def group by 83 and 87% in the F2 and F3 generations, respectively. In the Morris water maze, the n-3 Def group showed a longer escape latency and delayed acquisition of this task compared with the n-3 Adq group in both generations. The acquisition and memory levels of the n-3 Def group in the F3 generation seemed to be lower than that of the F2 generation. The 22:5n-6/22:6n-3 ratio in the frontal cortex and dams' milk was markedly increased in the n-3 Def group, and this ratio was significantly higher in the F3 generation compared with the F2 generation. These results suggest that learning and cognitive behavior are related to brain DHA status, which, in turn, is related to the levels of the milk/dietary n-3 fatty acids.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1471-4159.2000.0752563.x

Behavioral Deficits Associated with Dietary Induction of Decreased Brain Docosahexaenoic Acid Concentration

Studies were carried out to determine if decreased levels of central nervous system docosahexaenoic acid (DHA), a result of consuming an n-3-deficient diet, had an effect on learning- and memory-related behaviors in adult male rats. Females were reared on an n-3-deficient or n-3-adequate diet beginning at 21 d of life. Their male pups, the F2 generation, were weaned to the diet of the dam and tested at 9–12 wk of age. An olfactory-based discrimination and Morris water maze task were used to assess performance. Whole brain was collected after the behavioral experiments and central nervous system fatty acid content was analyzed in olfactory bulb total lipid extracts. F2 generation male rats consuming the n-3-deficient diet had an 82% decrease in DHA compared to rats consuming the n-3-adequate diet. The n-3-deficient animals made significantly more total errors in a 7-problem, 2-odor discrimination task compared to the n-3-adequate group. Furthermore, the escape latency in the Morris water maze task was significantly longer for the n-3-deficient rats compared to the n-3-adequate rats. These results indicate that rats with decreased DHA levels in the central nervous system perform poorer in these tasks compared to rats with higher DHA levels and suggest the presence of learning deficits in these animals.

Rats with low levels of brain docosahexaenoic acid show impaired performance in olfactory-based and spatial learning tasks.

This study investigated the influence of brain docosahexaenoic acid (DHA) deficiency on simple and complex olfactory-based learning and memory in 2nd generation (F2) adult male rats. Rats raised and maintained on either an n-3-adequate or an n-3-deficient diet were tested for acquisition of an olfactory learning set and an olfactory memory task, and for motivation to obtain a water reward. Despite a 76% decrease in brain DHA, n-3-deficient rats were able to acquire most simple 2-odor discrimination tasks but were deficient in the acquisition of a 20-problem olfactory learning set. This deficit could not be attributed to changes in sensory capacity but, instead, appeared to represent a deficit in higher order learning.

https://psycnet.apa.org/journals/bne/116/6/1022.pdf

Cognitive deficits in docosahexaenoic acid-deficient rats.

We have previously shown that the docosahexaenoate (22:6n-3) status in membrane phospholipids influences the biosynthesis and accumulation of phosphatidylserine (PS) in brain microsomes and C6 glioma cells. In the present study, we investigated whether the observed effect of membrane docosahexaenoic acid status on PS accumulation is universal or occurs specifically in neuronal tissues. We observed that rat brain cortex, brain mitochondria, and olfactory bulb, where 22:6n-3 is highly concentrated, contain significantly higher levels of PS in comparison to liver and adrenal, where 22:6n-3 is a rather minor component. Phospholipid molecular species analysis revealed that in brain cortex, mitochondria, and olfactory bulb 18:0,22:6n-3 was the most abundant species representing 45-65% of total PS. In nonneuronal tissues such as liver and adrenal, 18:0,20:4n-6 was the major PS species. Dietary depletion of n-3 fatty acids during prenatal and postnatal developmental periods decreased the brain 22:6n-3 content by more than 80%, with a concomitant increase in 22:5n-6 in all tissues. Under these conditions, an approximately 30-35% reduction in total PS in rat brain cortex, brain mitochondria, and olfactory bulb was observed, while PS levels in liver and adrenal were unchanged. The observed reduction of PS content in neuronal membranes appears to be due to a dramatic reduction of 18:0,22:6n-3-PS without complete replacement by 18:0,22:5n-6-PS. These results establish that variations in membrane 22:6n-3 fatty acid composition have a profound influence on PS accumulation in neuronal tissues where 22:6n-3 is abundant. These data have implications in neuronal signaling events where PS is believed to play an important role.

n−3 Fatty acid deficiency decreases phosphatidylserine accumulation selectively in neuronal tissues

We applied our in vivo fatty acid method to examine concentrations, incorporation, and turnover rates of docosahexaenoic acid (22:6 n-3) in brains of rats subject to a dietary deficiency of alpha-linolenic acid (18:3 n-3) for three generations. Adult deficient and adequate rats of the F3 generation were infused intravenously with [4, 5-(3)H]docosahexaenoic acid over 5 min, after which brain uptake and distribution of tracer were measured. Before infusion, the plasma 22:6 n-3 level was 0.2 nmol ml(-1) in 18:3 n-3-deficient compared with 10.6 nmol ml(-1) in control rats. Brain unesterified 22:6 n-3 was not detectable, whereas docosahexaenoyl-CoA content was reduced by 95%, and 22:6 n-3 content in different phospholipid classes was reduced by 83-88% in deficient rats. Neither plasma or brain arachidonic acid (20:4 n-6) level was significantly changed with diet. Docosapentaenoic acid (22:5 n-6) reciprocally replaced 22:6 n-3 in brain phospholipids. Calculations using operational equations from our model indicated that 22:6 n-3 incorporation from plasma into brain was reduced 40-fold by 18:3 n-3 deficiency. Recycling of 22:6 n-3 due to deacylation-reacylation within phospholipids was reduced by 30-70% with the deficient diet, but animals nevertheless continued to produce 22:6 n-3 and docosahexaenoyl-CoA for brain function. We propose that functional brain effects of n-3 deficiency reflect altered ratios of n-6 to n-3 fatty acids.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1471-4159.2000.0752392.x

Nutritional Deprivation of α‐Linolenic Acid Decreases but Does Not Abolish Turnover and Availability of Unacylated Docosahexaenoic Acid and Docosahexaenoyl‐CoA in Rat Brain

Rebecca Sheaff Greiner

Papers

Behavioral Deficits Associated with Dietary Induction of Decreased Brain Docosahexaenoic Acid Concentration

Rats with low levels of brain docosahexaenoic acid show impaired performance in olfactory-based and spatial learning tasks.

Cognitive deficits in docosahexaenoic acid-deficient rats.

n−3 Fatty acid deficiency decreases phosphatidylserine accumulation selectively in neuronal tissues

Nutritional Deprivation of α‐Linolenic Acid Decreases but Does Not Abolish Turnover and Availability of Unacylated Docosahexaenoic Acid and Docosahexaenoyl‐CoA in Rat Brain