Neuroscience
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Valproic acid (VPA), a branched short-chain fatty acid, is generally used as an antiepileptic drug and a mood stabilizer. VPA is a relatively safe drug, but its use in higher concentrations is associated with idiosyncratic neurotoxicity. Investigations involving cerebral cortex and cerebellum can shed light on whether neurotoxicity induced by branched chain fatty acids like VPA is mediated by oxidative stress. ⋯ Some neurotoxicity biomarkers were investigated in which the activity of acetylcholinesterase (AChE) and sodium-potassium ATPase (Na(+), K(+)-ATPase) was decreased and monoamine oxidase (MAO) was increased. These results indicate that VPA induces oxidative stress by compromising the antioxidant status of the neuronal tissue. Further studies are required to decipher the cellular and molecular mechanisms of branched chain fatty acid-induced neurotoxicity.
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Drinking alcohol in moderation is often considered a health-conscious behavior, associated with improved cardiovascular and brain health. However, "moderate" amounts of alcohol include drinking 3-4 alcohol beverages in a day, which is closer to binge drinking and may do more harm than good. Here we examined how daily drinking of moderate-high alcohol alters the production of new neurons in the adult hippocampus. ⋯ Therefore, moderate alcohol consumption did not disrupt basic sensory, motor or learning processes. However, the number of cells produced in the dentate gyrus of the hippocampus was reduced by nearly 40%. Thus, even moderate consumption of alcohol for a relatively short period of time can have profound effects on structural plasticity in the adult brain.
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We propose a novel reduced-order neuronal network modeling framework that includes an enhanced firing rate model and a corresponding synaptic calcium-based synaptic learning rule. Specifically, we propose enhancements to the Wilson-Cowan firing-rate neuron model that permit full spike-frequency adaptation seen in biological lateral amygdala (LA) neurons, while being sufficiently general to accommodate other spike-frequency patterns. We also report a technique to incorporate calcium-dependent plasticity in the synapses of the network using a regression scheme to link firing rate to postsynaptic calcium. ⋯ The framework was then used to develop a larger LA network model to investigate the roles of tone and shock distributions and of intrinsic connectivity in auditory fear learning. The model suggested combinations of tone and shock densities that would provide experimental estimates of tone responsive and conditioned cell proportions. Furthermore, it provided several insights including how intrinsic connectivity might help distribute sensory inputs to produce conditioned responses in cells that do not directly receive both tone and shock inputs, and how a balance between potentiation of excitation and inhibition prevents stimulus generalization during fear learning.
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Valproate (VPA) is an anticonvulsant and mood-stabilizing drug. It is a broad-spectrum histone deacetylase inhibitor with neuroprotective effects. We investigated whether VPA reduces retinal neuronal death induced by optic nerve crush (ONC). ⋯ Furthermore, VPA upregulated levels of bcl-2, BDNF, TrkB in the retina post-injury. VPA and SB treatment resulted in the hyperacetylation of histone H3K14, attenuated histone H3K9 hypermethylation in the BDNF promoter, and promoted transcriptional activity. These results demonstrate that VPA appears to protect RGCs from ONC by inhibiting neuronal apoptosis possibly via the activation of BDNF-TrkB signaling and HDAC inhibition.
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Associative learning can enable cues from the environment to stimulate feeding in the absence of physiological hunger. How learned cues are integrated with the homeostatic regulatory system is unknown. Here we examined whether the underlying mechanism involves the hypothalamic orexigenic neuropeptide regulators orexin/hypocretin (ORX) and melanin-concentrating hormone (MCH). ⋯ In contrast, there were very few MCH neurons with Fos induction in both the Paired and Unpaired conditions. Thus, the food-cue selectively induced Fos in ORX but not in MCH neurons. These results suggest a role for ORX in cue-induced feeding that occurs in the absence of physiological hunger.