Neuroscience
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Seizure susceptibility to neurological insults, including chemical convulsants, is age-dependent and most likely reflective of overall differences in brain excitability. The molecular and cellular mechanisms underlying development-dependent seizure susceptibility remain to be fully understood. Because the mammalian target of rapamycin (mTOR) pathway regulates neurite outgrowth, synaptic plasticity and cell survival, thereby influencing brain development, we tested if exposure of the immature brain to the mTOR inhibitor rapamycin changes seizure susceptibility to neurological insults. ⋯ Additionally, rapamycin treatment down-regulates the expression of potassium-chloride cotransporter 2 (KCC2) in the thalamus and to a lesser degree in the hippocampus. Pharmacological inhibition of thalamic mTOR or KCC2 increases susceptibility to pilocarpine-induced seizure in immature rats. Thus, our study suggests a role for the mTOR pathway in age-dependent seizure susceptibility.
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Exploration of the molecular dynamics underlying regeneration in the central nervous system of regeneration-competent organisms has received little attention thus far. By combining a cerebellar lesion paradigm with differential proteome analysis at a post-lesion survival time of 30 min, we screened for protein candidates involved in the early stages of regeneration in the cerebellum of such an organism, the teleost fish Apteronotus leptorhynchus. Out of 769 protein spots, the intensity of 26 spots was significantly increased by a factor of at least 1.5 in the lesioned hemisphere, relative to the intact hemisphere. ⋯ Proteins whose abundance was significantly increased include: erythrocyte membrane protein 4.1N, fibrinogen gamma polypeptide, fructose-biphosphate aldolase C, alpha-internexin neuronal intermediate filament protein, major histocompatibility complex class I heavy chain, 26S proteasome non-ATPase regulatory subunit 8, tubulin alpha-1C chain, and ubiquitin-specific protease 5. Proteins with significantly decreased levels of abundance include: brain glycogen phosphorylase, neuron-specific calcium-binding protein hippocalcin, and spectrin alpha 2. We hypothesize that these proteins are involved in energy metabolism, blood clotting, electron transfer in oxidative reactions, cytoskeleton degradation, apoptotic cell death, synaptic plasticity, axonal regeneration, and promotion of mitotic activity.
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It is well known that the preoptic-anterior hypothalamus (PO/AH), containing temperature-sensitive and -insensitive neurons plays an important role in precise thermoregulatory responses. Previous in vivo studies suggest that the arginine vasopressin (AVP) is an important endogenous mediator in thermoregulation, since AVP and V(1a) vasopressin receptor antagonist can induce hypothermia and hyperthermia, respectively. In the present study, intracellular electrophysiological activity was recorded from temperature-sensitive and -insensitive neurons in rat PO/AH tissue slices, using a whole-cell patch clamp. ⋯ V(1a) vasopressin receptor participated in these responses. Since excited warm-sensitive neurons or inhibited cold-sensitive and temperature-insensitive neurons promote heat loss or suppress heat production and retention. These results that AVP excites warm-sensitive neurons and inhibits cold-sensitive and temperature-insensitive neurons suggest a probable mechanism of AVP-induced hypothermia.
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Multiple sclerosis (MS) is characterized by inflammatory process associated with nitric oxide (NO) and the related species production in CNS, which can nitrosylate protein thiols and modulate their structure and functions, also reducing the CNS content of redox active compounds, such as glutathione (GSH). We have evaluated the relationships between S-nitrosothiols (RSNO) and GSH in the experimental model of MS - experimental autoimmune encephalomyelitis (EAE), during the treatment with inducible NO synthase inhibitor - aminoguanidine (AG) and thiol donor molecule - N-acetyl-L-cysteine (NAC). ⋯ The findings of our work suggest a potential role of RSNO and GSH in early clinical presentation of experimental MS, that might be also useful as predictive parameters for MS treatment directed to increased GSH and thiol pool in CNS.
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One of the benefits musicians derive from their training is an increased ability to detect small differences between sounds. Here, we asked whether musicians' experience discriminating sounds on the basis of small acoustic differences confers advantages in the subcortical differentiation of closely related speech sounds (e.g., /ba/ and /ga/), distinguishable only by their harmonic spectra (i.e., their second formant trajectories). Although the second formant is particularly important for distinguishing stop consonants, auditory brainstem neurons do not phase-lock to its frequency range (above 1000 Hz). ⋯ By measuring the degree to which subcortical response timing differs to the speech syllables /ba/, /da/, and /ga/ in adult musicians and nonmusicians, we reveal that musicians demonstrate enhanced subcortical discrimination of closely related speech sounds. Furthermore, the extent of subcortical consonant discrimination correlates with speech-in-noise perception. Taken together, these findings show a musician enhancement for the neural processing of speech and reveal a biological mechanism contributing to musicians' enhanced speech perception in noise.