Neurobiology of disease
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Neurobiology of disease · Mar 2012
NO-dependent protective effect of VEGF against excitotoxicity on layer VI of the developing cerebral cortex.
In industrialized countries, cerebral palsy affects 2.5‰ of preterm and term infants. At a neurochemical level, the massive release of glutamate constitutes a major process leading to excitotoxicity and neonatal brain lesions. Previous studies, conducted in the laboratory, revealed that, in (δ/δ)VEGF(A) transgenic mice, glutamate-induced brain lesions are exacerbated suggesting that VEGF(A) could play a protective action against excitotoxicity. ⋯ A short-term glutamate treatment increased nNOS Ser1412 phosphorylation, while a long-term exposure inhibited nNOS/NR2B protein-protein interactions. Altogether, these findings indicate that, in deep cortical layers of mice neonates, glutamate stimulates nNOS activity. Contrasting with mature brain, NO production induced by high concentrations of glutamate is neuroprotective and is required for the anti-necrotic effect of VEGF(A).
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Neurobiology of disease · Mar 2012
The beneficial effects of regular exercise on cognition in REM sleep deprivation: behavioral, electrophysiological and molecular evidence.
Inadequate sleep is prevalent in modern societies and is known to profoundly impair cognitive function. We examined the impact of 4 weeks of regular treadmill exercise on sleep deprivation induced spatial learning and memory, synaptic plasticity and related signaling molecules in area CA1 of the rat hippocampus. Rats were exercised on a treadmill and subsequently sleep-deprived for 24h using the modified multiple platform technique. ⋯ Extracellular recording from area CA1 of anesthetized rats revealed that early phase LTP (E-LTP) was markedly impaired in the sedentary sleep deprived animals, but was normal in the exercised sleep deprived group. Additionally, immunoblot analysis of CA1 area before (basal) and after expression of E-LTP indicated that the significant down-regulation of the brain derived neurotrophic factor (BDNF) and phosphorylated calcium-calmodulin dependent protein kinase II (P-CaMKII) levels in sleep deprived animals was prevented by the regular exercise regimen. The results suggest that the regular exercise protocol prevents the sleep deprivation induced impairments in short-term memory and E-LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CaMKII and BDNF associated with sleep deprivation.
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Neurobiology of disease · Mar 2012
The abolishment of anesthesia-induced cognitive impairment by timely protection of mitochondria in the developing rat brain: the importance of free oxygen radicals and mitochondrial integrity.
Early exposure to general anesthesia (GA) causes developmental neuroapoptosis in the mammalian brain and long-term cognitive impairment. Recent evidence suggests that GA also causes functional and morphological impairment of the immature neuronal mitochondria. Injured mitochondria could be a significant source of reactive oxygen species (ROS), which, if not scavenged in timely fashion, may cause excessive lipid peroxidation and damage of cellular membranes. ⋯ The subiculum is highly intertwined with the hippocampal CA1 region, anterior thalamic nuclei, and both entorhinal and cingulate cortices; hence, it is important in cognitive development. We found that PPX or EUK-134 co-treatment completely prevented GA-induced cognitive impairment. Because mitochondria are vulnerable to GA-induced developmental neurotoxicity, they could be an important therapeutic target for adjuvant therapy aimed at improving the safety of commonly used GAs.
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Neurobiology of disease · Mar 2012
P2X7 receptor blockade prevents ATP excitotoxicity in neurons and reduces brain damage after ischemia.
Overactivation of subtype P2X7 receptors can induce excitotoxic neuronal death by calcium (Ca(2+)) overload. In this study, we characterize the functional properties of P2X7 receptors using electrophysiology and Ca(2+) monitoring in primary cortical neuron cultures and in brain slices. Both electrical responses and Ca(2+) influx induced by ATP and benzoyl-ATP were reduced by Brilliant Blue G (BBG) at concentrations which specifically inhibit P2X7 receptors. ⋯ Treatment with BBG (twice per day, 30 mg/kg) produced a 60% reduction in the extent of brain damage compared to treatment with vehicle alone. These results show that P2X7 purinergic receptors mediate tissue damage after OGD in neurons and following transient brain ischemia. Therefore, these receptors are a relevant molecular target for the development of new treatments to attenuate brain damage following stroke.