Neuroscience
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Brain-derived neurotrophic factor (BDNF) release to nerve terminals in the central nervous system is crucial in synaptic transmission and neuronal plasticity. However, BDNF release peripherally from primary afferent neurons has not been investigated. In the present study, we show that BDNF is synthesized by primary afferent neurons located in the dorsal root ganglia (DRG) in rat, and releases to spinal nerve terminals in response to depolarization or visceral inflammation. ⋯ These results suggest a possibility of pro-proliferative effect in the inflamed bladder. Consistently we show that the proliferation marker Ki67 expression levels are enhanced in the inflamed organ. Our results imply that in vivo BDNF release to the peripheral organ is an important event in neurogenic inflammatory state.
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Multiple sclerosis is a demyelinating disease with severe neurological symptoms due to blockage of signal conduction in affected axons. Spontaneous remyelination via endogenous progenitors is limited and eventually fails. Recent reports showed that forced expression of some transcription factors within the brain converted somatic cells to neural progenitors and neuroblasts. ⋯ Moreover, transdifferentiation of some Oct4-transfected cells (GFP+ cells) to Olig2+ and CNPase+ cells was confirmed by immunostaining. One-week administration of VPA followed by one-week forced expression of Oct4 enhanced myelination by converting transduced cells to myelinating oligodendrocytes. This finding seems promising for enhancing myelin repair within the adult brains.
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The mesocorticolimbic dopamine system, originating in the ventral tegmental area (VTA) is normally constrained by GABA-mediated synaptic inhibition. Accumulating evidence indicates that long-term potentiation of GABAergic synapses (LTPGABA) in VTA dopamine neurons plays an important role in the actions of drugs of abuse, including ethanol. We previously showed that a single infusion of glycine into the VTA of rats strongly reduces ethanol intake for 24h. ⋯ By contrast, glycine pretreatment did not prevent potentiation of inhibitory postsynaptic currents (IPSCs) during a continuous exposure to the nitric oxide (NO) donor, SNAP (S-nitroso-N-acetylpenicillamine), or a brief exposure to 10 μM glycine and 10 μM NMDA (N-methyl-D-aspartate), an agonist of NMDA-type glutamate receptors. Thus, the blockade of LTPGABA by glycine is probably resulted from suppressing glutamate release by activating the GlyRs on the glutamatergic terminals. This effect of glycine may contribute to the reduction in ethanol intake induced by intra-VTA glycine observed in vivo.
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Review
Influence of a visual-verbal Stroop test on standing and walking performance of older adults.
The dual task (DT) paradigm has been used to investigate decrements in balance performance while walking and standing in fall prevention studies with older adults. However, there are inconsistent findings whether balance performance decreases or increases in DT situations. Following different theoretical models (e.g. limited resource hypothesis or cross domain competition model), these inconsistent findings can be explained by task settings and task complexity. ⋯ Moreover, not all modified gait variables could be defined as negative DT costs. Increased SW and decreased step length might be used to compensate influences on lateral stability while demands on motor-cognitive resources increase. Further, drawing conclusions from a standing task for walking conditions might lead to misinterpretations.
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Microglia, the resident immune cells in the central nervous system (CNS), constantly survey the surrounding neural parenchyma and promptly respond to brain injury. Activation of purinergic receptors such as P2Y12 receptors (P2Y12R) in microglia has been implicated in chemotaxis toward ATP that is released by injured neurons and astrocytes. Activation of microglial P2Y12R elicits outward potassium current that is associated with microglial chemotaxis in response to injury. ⋯ This current was abolished in microglia obtained from mice lacking P2Y12R. Dissecting the properties of the P2Y12R-mediated current using a pharmacological approach revealed that both the ATP and neuronal injury-induced outward current in microglia was sensitive to quinine (1mM) and bupivacaine (400μM), but not tetraethylammonium (TEA) (10mM) and 4-aminopyridine (4-AP) (5mM). These results suggest that the quinine/bupivacaine-sensitive potassium channels are the functional effectors of the P2Y12R-mediated signaling in microglia activation following neuronal injury.