Neuroscience
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Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase and activates peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) which attenuates oxidative damage. Alpha-lipoic acid (ALA) has been proven to protect the rat brain against cerebral ischemia injury by reducing oxidative stress. However, the underlying mechanisms are poorly understood. In this study, we investigated the potential neuroprotection and the possible role of ALA in SIRT1 pathway. ⋯ ALA protected the mouse brain against ischemic damage, and this protection may be through up-regulating SIRT1-dependent PGC-1α expression.
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Caffeine, a methylated derivative of xanthine and widely consumed psychoactive substance, acts in several targets in the nervous system. We investigated its role in retinal explants of chick embryo analyzing the role of purinergic receptors in [(3)H]-GABA release induced by d-aspartate (d-asp). d-Asp increases GABA-release 4.5-fold when compared to basal levels from 13-day-old chick embryo retinal explants. Caffeine 500μM elevated d-asp-induced GABA release in 60%. ⋯ The GluN2B subunit-containing NMDAR antagonist ifenprodil inhibited the caffeine effect. Our results suggest that caffeine potentiates d-asp-induced GABA release, which is mediated by GAT-1, via inhibition of adenosine A1 receptor and activation of the PKA pathway. Regulation of NMDAR by phosphorylation of GluN2B subunit by a SFK may also be involved in the effect promoted by caffeine.
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P450 metabolic enzymes are expressed in the human and rodent brain. Recent data support their involvement in the pathophysiology of epilepsy. However, the determinants of metabolic enzyme expression in the epileptic brain are unclear. ⋯ Our data indicate that the effect of acute SE on brain CYP2E1 expression is localized and cell specific. Exposure to selected anti-epileptic drugs could play a role in determining CYP2E1 brain expression. Additional investigation is required to fully reproduce the culprits of P450 enzyme expression as observed in the human epileptic brain.
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Hippocampal neurons must maintain control over cytosolic calcium levels, especially during development, as excitation and calcium flux are necessary for proper growth and function. But excessive calcium can lead to excitotoxic cell death. Previous work suggests that neonatal male and female hippocampal neurons regulate cytosolic calcium differently, thereby leading to differential susceptibility to excitotoxic damage. ⋯ Surprisingly, there was no sex difference in the level of any of the three proteins. Treatment with DHT significantly decreased PMCA1 and NCX1, but increased SERCA2 protein levels in very young animals but not at a later timepoint. Taken together, these data suggest a complex interaction of sex, hormones, calcium regulation and developmental age; however androgens acting during the first week of life are implicated in regulation of hippocampal cell death and may be an underlying mechanism for sexually dimorphic apoptosis.
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Sensory experience has a profound effect on neocortical neurons. Passive stimulation of whiskers or sensory deprivation from whiskers can induce long-lasting changes in neuronal responses or modify the receptive field in adult animals. We recorded barrel cortical neurons in urethane-anesthetized rats in layers 2/3 or 5/6 to determine if repetitive stimulation would induce long-lasting response facilitation. ⋯ Inactivation of layer 2/3 also blocked response facilitation in layer 5/6, suggesting that layer 2/3 may be fundamental in this synaptic plasticity processes. Moreover, i.p. injection of eserine augmented the number of layer 2/3 neurons expressing long-lasting response facilitation; this effect was blocked by atropine, suggesting that muscarinic receptor activation favors the induction of the response facilitation. Our data indicate that physiologically repetitive stimulation of a single whisker at the frequency at which rats move their whiskers during exploration of the environment induces long-lasting response facilitation improving sensory processing.