Dietary variation of protein–carbohydrate: Effect on hypothalamic and hippocampal GABA–glutamate in relation to aging
TL;DR: The results suggest that an age-associated change in GABA–glutamate metabolism depends on the amount of dietary protein and carbohydrate and also on the brain region.
Abstract: Dietary protein variation has been found to alter brain regional neurochemistry with aging. In the present investigation, we studied the effect of short-term treatment of protein-carbohydrate variable diet to rat on hypothalamic and hippocampal gamma-amino butyric acid (GABA)-glutamate metabolism with increase of age. Exposure of male albino rats with diet containing normal protein (20%)-normal carbohydrate (68%) increased GABA metabolism and decreased glutamate metabolism in both hypothalamus and hippocampus with the increase of age. GABA-glutamate metabolism of rats having low protein (8%)-high carbohydrate (80%) diet for short-term period (STP), was activated in young age (3 months) and decreased in old age (18 months) in both the brain regions. On the contrary, intake of high protein (50%)-low carbohydrate (38%) diet under similar condition decreased GABA-glutamate metabolism in both hypothalamus and hippocampus of young brain and increased only in hypothalamus of aged brain. In hippocampus of aged brain the same diet decreased glutamate metabolism without changing its GABA metabolism. These results suggest that an age-associated change in GABA-glutamate metabolism depends on the amount of dietary protein and carbohydrate and also on the brain region.
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TL;DR: It is suggested that aging down-regulates brain regional GABA system with an up-regulation of corticosterone status and impairment of cognitive function and CR diet consumption improves this aging-induced deregulation of brain Regional GABA system, cortic testosterone status, and cognitive function.
14 citations
TL;DR: It may be suggested that long-term consumption of LP–HC and HP–LC diets modulate the brain regional glutamatergic activity reversibly with age.
Abstract: Glutamatergic activity of hypothalamus and hippocampus of young (3 months) male albino rats having normal diet [protein (20%)–carbohydrate (68%)] was increased with the increase of age. Long-term (60 consecutive days) feeding of low protein (8%)–high carbohydrate (80%) diet (LP–HC) increased glutamatergic activity in these brain regions of young rats and decreased that in aged (18 months). On the contrary, supplementation of high protein (50%)–low carbohydrate (38%) diet (HP–LC) under similar condition decreased glutamatergic activity in those brain regions of young and increased that in aged brain regions. Thus, prolonged exposure of LP–HC diet may damage young brain; whereas, HP–LC diet under similar condition causes excitotoxicity to aged brain. Therefore, considering the present scenario in relation to metabolism and receptor activity of glutamatergic system, it may be suggested that long-term consumption of LP–HC and HP–LC diets modulate the brain regional glutamatergic activity reversibly with age.
3 citations
Cites background from "Dietary variation of protein–carboh..."
...also indicated that short-term exposure to variable protein–carbohydrate containing diets modulates brain regional GABA–glutamate with age [22]....
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...Decrease in the ratio of the activity of glutamine synthetase/glutaminase with an increase of that in glutaminase/GAD (Table 3) suggest that there may be a decrease in glial glutamate with an increase of neuronal glutamate level [22] that is further mobilized to GABA by enhancing neuronal GAD activity (Fig....
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...1) in those two brain regions, further suggest that long-term intake of LP–HC diet may increase neuronal glutamate with a decrease in glial glutamate of young rats [22]....
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...Our recent past observations also indicated that short-term exposures to the diets having variable protein– carbohydrate alter brain regional GABA glutamate metabolism with age [22]....
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TL;DR: In this paper, the effect of dietary calorie restriction (CR) on the aging-related alteration of the immune response in male albino Wistar rats at the level of lymphocyte viability, proliferation, cytotoxicity, and DNA fragmentation in blood, spleen, and thymus and cytokines (IL-6, IL-10, and TNF-α) in different brain-regions.
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TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
289,852 citations
TL;DR: The evidence for glutamate as a transmitter at the locust neuromuscular junction has recently been carefully evaluated by Usherwood (1981), and it is shown that mechanisms exist that will terminate transmitter action rapidly.
Abstract: Glutamate is ubiquitously distributed in brain tissue, where it is present in a higher concentration than any other amino acid. During the last 50 years glutamate in brain has been the subject of numerous studies, and several different functions have been ascribed to it. Early studies by Krebs (1935) suggested that glutamate played a central metabolic role in brain. The complex compartmentation of glutamate metabolism in brain was first noted by Waelsch and coworkers (Berl et al., 1961). These studies were precipitated by the claim that glutamate improved mental behaviour and was beneficial in several neurological disorders including epilepsy and mental retardation. Other scientists pointed out its function in the detoxification of ammonia in brain (Weil-Malherbe, 1950). Glutamate is also an important building block in the synthesis of proteins and peptides, including glutathione (Meister, 1979). The toxic effect of administered glutamate and its analogues kainic acid, ibotenic acid, and N-methyl aspartic acid on CNS neurones has become a large and independent line of research (Lucas and Newhouse, 1957; Olney et al., 1974; Lund-Karlsen and Fonnum, 1976; Coyle, 1983). Attention has also been focused on the role of glutamate as a precursor for the inhibitory neurotransmitter y-aminobutyric acid (GABA) (Roberts and Frankel, 1950). Electrophysiological studies (Curtis and Watkins, 1961) focused early on the powerful and excitatory action of glutamate on spinal cord neurones. Since the action was widespread and effected by both the Dand Lforms, it was at first difficult to believe that glutamate could be a neurotransmitter. During the last 15 years, however, several studies have provided support for the concept that glutamate is a transmitter in brain (for review see Curtis and Johnston, 1974; Fonnum, 1978; 1981; Roberts et al., 1981; DiChiara and Gessa, 1981). Glutamate satisfies today to a large extent the four main criteria for classification as a neurotransmitter: (1) it is presynaptically localized in specific neurones; (2) it is specifically released by physiological stimuli in concentrations high enough to elicit postsynaptic response; (3) it demonstrates identity of action with the naturally occurring transmitter, including response to antagonists; and (4) mechanisms exist that will terminate transmitter action rapidly. The evidence for glutamate as a transmitter at the locust neuromuscular junction has recently been carefully evaluated by Usherwood (1981). In that case the identity of action of glutamate with the naturally occurring transmitter on the neuromuscular receptor, the release from nerve terminals, and its similarity to acetylcholine at the mammalian neuromuscular junction with regard to presynaptic pharmacology and denervation supersensitivity are compelling evidence for glutamate as a neurotransmitter. The main methods used to identify glutamergic pathways in brain will be critically reviewed and discussed. The effect of lesions on high-affinity uptake and release are particularly important, but immunohistochemical methods to study enzymes and glutamate itself are becoming more interesting. The release of glutamate has been demonstrated by several different procedures using both in vivo and in vitro preparations. The synthesis of large groups of specific agonists and antagonists has been important both for identification and characterization of the glutamate receptor by electrophysiological techniques and for the isolation of glutamate receptors. High and perhaps low-affinity uptake into nerve terminals and glial cells is important for the termination of transmitter action. Particular attention is given in this review to the complex compartmentation of glutamate synthesis and the possibility of identifying the transmitter pool of glutamate.
1,997 citations
TL;DR: Differences in gene expression in the hypothalamus and cortex of young and aged mice are examined by using high-density oligonucleotide arrays to identify key genes involved in neuronal structure and signaling and suggest their roles in learning and memory.
Abstract: A better understanding of the molecular effects of aging in the brain may help to reveal important aspects of organismal aging, as well as processes that lead to age-related brain dysfunction. In this study, we have examined differences in gene expression in the hypothalamus and cortex of young and aged mice by using high-density oligonucleotide arrays. A number of key genes involved in neuronal structure and signaling are differentially expressed in both the aged hypothalamus and cortex, including synaptotagmin I, cAMP-dependent protein kinase C β, apolipoprotein E, protein phosphatase 2A, and prostaglandin D. Misregulation of these proteins may contribute to age-related memory deficits and neurodegenerative diseases. In addition, many proteases that play essential roles in regulating neuropeptide metabolism, amyloid precursor protein processing, and neuronal apoptosis are up-regulated in the aged brain and likely contribute significantly to brain aging. Finally, a subset of these genes whose expression is affected by aging are oppositely affected by exposure of mice to an enriched environment, suggesting that these genes may play important roles in learning and memory.
316 citations
TL;DR: It has been found that certain amino acids and indole derivatives, when allowed to react with ninhydrin at an alkaline pHS, form highly fluorescent products that can be measured in as little as 3 ,ug dry weight of brain tissue.
Abstract: THE uniquely high activity of glutamic decarboxylase (GDC)? in brain has been reported (ROBERTS, 1950; WINGO and AWAPARA, 1950). ROBERTS (1956), using pooled tissues, has shown that there is a fiveto six-fold greater activity of GDC in grey matter than in white matter of the cat brain. Because of the limitations of the manometric methods used, further resolution of the cytoarchitectonic distribution of GDC has awaited the development of more sensitive analytical methods for measuring the activity of this enzyme. It has been found that certain amino acids and indole derivatives, when allowed to react with ninhydrin at an alkaline pHS, form highly fluorescent products. Of the substances tested, under the conditions to be described, y-aminobutyric acid (yAB) has given the greatest amount of fluorescence and can be measured at a concentration of lo-' M. A fluorescence method has been developed to measure the activity of GDC in as little as 3 ,ug dry weight of brain tissue. The activity of this enzyme has been measured in various areas of the monkey and rabbit brain as well as in the whole brain of mouse and rat. The histochemical distribution of GDC in the layers of the monkey cerebellar cortex and selected white tracts of the rabbit and rat has also been determined. White matter has been shown to be extremely poor in GDC.
311 citations
TL;DR: Evidence is accumulating that, in the brain, the amino–acids L-glutamate and γ-aminobutyric acid (GABA) are essential agents of communication and not just elements of an alternate metabolic pathway, as was generally believed for some years.
Abstract: Evidence is accumulating that, in the brain, the amino–acids L-glutamate and γ-aminobutyric acid (GABA) are essential agents of communication and not just elements of an alternate metabolic pathway, as was generally believed for some years.
258 citations