Neuroscience
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Hyperpolarisation-activated (Ih) currents are considered important for dendritic integration, synaptic transmission, setting membrane potential and rhythmic action potential (AP) discharge in neurons of the central nervous system. Hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels underlie these currents and are composed of homo- and hetero-tetramers of HCN channel subunits (HCN1-4), which confer distinct biophysical properties on the channel. Despite understanding the structure-function relationships of HCN channels with different subunit stoichiometry, our knowledge of their expression in defined neuronal populations remains limited. ⋯ This HCN4 expression profile in inhibitory interneurons mirrors both the prevalence of Ih sub-threshold currents and high-frequency AP discharge. Our findings indicate that HCN4 subunits are expressed in several populations of spinal and hippocampal interneurons, which are known to express both Ih sub-threshold currents and exhibit high-frequency AP discharge. As HCN channel function plays a critical role in pain perception, learning and memory, and sleep as well as the pathogenesis of several neurological diseases, these findings provide important insights into the identity and neurochemical status of cells that could underlie such conditions.
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Growing evidence has suggested that hydrogen sulfide (H₂S) acts as a novel neuro-modulator and neuroprotective agent; however, it remains to be investigated whether H2S has a direct effect on neural stem cells (NSCs). We report here that NSCs expressed cystathionine β synthase (CBS) and addition of exogenous H2S donor, L-cysteine, stimulated proliferation and increased the differentiation potential of NSCs to neurons and astroglia. ⋯ Further analysis revealed that L-cysteine-induced proliferation was associated with phosphorylation of extracellular signal-regulated kinases 1/2 and differentiation with altered expression of differentiation-related genes. Taken together, the present data suggest that L-cysteine can enhance proliferation and differentiation of NSCs via the CBS/H2S pathway, which may serve as a useful inference for elucidating its role in regulating the fate of NSCs in physiological and pathological settings.
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Physical exercise is known to produce beneficial effects to the nervous system. In most cases, brain-derived neurotrophic factor (BDNF) is involved in such effects. However, little is known on the role of BDNF in exercise-related effects on Parkinson's disease (PD). ⋯ Exercised groups exhibited reduced damage to the dopaminergic system, detected as a decreased drop of TH levels in SNc and CPu. On the other hand, BDNF blockade was capable of substantially reducing TH expression postlesion, implying enhanced dopaminergic cell loss. Our data revealed that physical exercise is capable of reducing the damage induced by 6-OHDA, and that BDNF receptors are involved in that effect.
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Recent developments in the technology to breed and house laboratory rodents for medical research has produced individually ventilated cage (IVC) systems. These IVC systems produce a cage environment significantly different to conventional cages. As it is not known in detail whether housing mice in IVCs impacts on their baseline and drug-induced behaviours compared to mice of conventional filter-top cages a comprehensive multi-tiered phenotyping strategy was used to test the behavioural consequences of IVC housing in male and female C57BL/6JArc mice. ⋯ In conclusion, researchers upgrading their holding facilities to IVC housing may encounter a shift in experimental outcomes (e.g. post pharmacological challenges) and the behavioural phenotype of test mice. Furthermore, differences between the housing conditions of breeding facilities and test facilities must carefully be considered. Finally, researchers should clarify in detail the type of housing test animals have been exposed to when publishing experimental animal research data.
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N-Methyl-d-aspartate receptor (NMDAR) antagonists mimic several symptoms of schizophrenia in healthy subjects, and are used in preclinical disease models. In the present study, the impact of pharmacologically and genetically induced NMDAR hypofunction was assessed in rats and mice, including the NMDAR hypomorphic (Grin1) mice, with respect to neuronal network oscillations. Field potentials were recorded from the ventro-medial prefrontal cortex (mPFC) and hippocampus (CA1) in rats, as well as spontaneous and elicited hippocampal theta oscillations in response to brainstem stimulation in Grin1 and wild-type (WT) mice under anesthesia. ⋯ Administration of MK-801 achieved high levels of NMDAR occupancy (84-98%) in both rats and mice, which is comparable to the approximately 90-95% reduction of NMDAR expression in the Grin1 mouse. Impaired elicited CA1 theta oscillation in WT mice following MK-801, or Grin1 mice was significantly improved by LY451395. These findings demonstrate similar, although not identical, changes in network activity following reduction in functioning NMDARs induced by acute pharmacological or genetic manipulations, indicating that these novel neurophysiological models could be used in evaluating drug candidates targeting glutamate neurotransmission.