Neuroscience
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Metformin a well known antidiabetic drug has been recently investigated and proposed to promote neurogenesis and enhance the spatial memory formation. In the present study, we aim to investigate the neuroprotective effect of metformin with respect to Parkinson's disease (PD). MPTP (Sigma-Aldrich, St. ⋯ TH-positive cells decreased up to 16% in MPTP-treated mice as compared to normal mice (P<0.001) and were found to be protected from degeneration in metformin-treated mice (47%, P<0.01). Interestingly, BDNF levels were found to be significantly elevated in metformin treatment group as compared to MPTP treatment mice (P<0.001). In conclusion, metformin possesses neuroprotective activity and provides preclinical support for therapeutic prospective of this compound in the treatment of PD.
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The normal function of GABAA receptor-mediated inhibition is governed by several factors, including release of GABA, subunit composition and density of the receptors and in particular by the appropriate ionic gradient. In the human epileptogenic neocortex an impaired chloride (Cl(-)) gradient has been proposed, due to decreases of potassium-coupled chloride transport (KCC2) and voltage-gated Cl(-) channels (ClC). Regarding sodium- and potassium-coupled Cl(-) transport (NKCC1) both up- and downregulations have been proposed. ⋯ In human neurons, DIDS increased τrec from 23.3 to 50.7s (n=7), corresponding to a DIDS-sensitive rate of 0.0200s(-1). These data suggest a greatly reduced KCC2-mediated transport rate in most of the human neurons. The two subgroups observed in human tissue indicate a considerable variability of Cl(-) transport within a given tissue from almost normal to greatly impeded, predominated by a decline of KCC2 whereas AE is unaltered.
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Chronic sleep restriction (CSR) has various negative consequences on cognitive performance and health. Using a rat model of CSR that uses alternating cycles of 3h of sleep deprivation (using slowly rotating activity wheels) and 1h of sleep opportunity continuously for 4 days ('3/1' protocol), we previously observed not only homeostatic but also allostatic (adaptive) sleep responses to CSR. In particular, non-rapid eye movement sleep (NREMS) electroencephalogram (EEG) delta power, an index of sleep intensity, increased initially and then declined gradually during CSR, with no rebound during a 2-day recovery period. ⋯ After 24h of recovery, BDNF levels were at the control levels. This time course of BDNF levels parallels the previously reported changes in NREMS delta power during the same CSR protocol. Changes in BDNF protein levels in the cortex and basal forebrain may be part of the molecular mechanisms underlying allostatic sleep responses to CSR.
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Neural networks ultimately arrive at functional output via interaction of the excitability of individual neurons and their synaptic interactions. We investigated the relationships between voltage-gated ion channel and neurotransmitter receptor mRNA levels in mouse spinal cord at four different postnatal time points (P5, P11, P17, and adult) and three different adult cord levels (cervical, thoracic, and lumbosacral) using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Our analysis and data visualization are novel in that we chose a focal group of voltage-gated channel subunits and transmitter receptor subunits, performed absolute quantitation of mRNA copy number for each gene from a sample, and used multiple correlation analyses and correlation matrices to detect patterns in correlated mRNA levels across all genes of interest. These correlation profiles suggest that postnatal maturation of the spinal cord includes changes among channel and receptor subunits that proceed from widespread co-regulation to more refined and distinct functional relationships.
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We investigated the involvement of neuropeptide Y (NPY) in the modulation of cholecystokinin-4 (CCK-4)-evoked anxiety and depression. Adult male mice were injected with vehicle, CCK-4, NPY, NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY or antagonist BIBP3226, via intracerebroventricular route, and subjected to social interaction or forced swim test (FST) for the evaluation of anxiety- and depression-like phenotypes, respectively. To assess the interactions between the two systems, if any, NPYergic agents were administered prior to CCK-4 and the animals were subjected to these behavioral tests. ⋯ Population of NPY-immunopositive cells was also decreased in the AcbSh, BSTLV, prefrontal cortex and hypothalamic arcuate nucleus (ARC). However, NPY-immunoreaction in the fibers of the ARC and cells of the central nucleus of amygdala was unchanged. We conclude that, inhibition of NPY signaling in the brain by CCK-4 might be causal to anxiety- and depression-like behaviors.