Neuroscience
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Ischemic postconditioning (PostC) is an endogenous neuroprotective strategy for cerebral ischemia induced by low activation of glutamate receptors. We have previously shown that the application of the mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine (DHPG) 5 min after 30 min of oxygen and glucose deprivation (OGD) reduces CA1 damage in organotypic hippocampal slices by activating the PI3K-Akt signalling pathway. In order to extend these data, we analysed the production of reactive oxygen species (ROS) and the glycogen synthase kinase 3β (GSK3β) signalling pathway. ⋯ This reduction was prevented by the PI3K inhibitor LY294002, indicating that there is a link between the PI3K/Akt pathway and the formation of ROS in the protective mechanisms of PostC. DHPG PostC also induces a transient increased in GSK3β phosphorylation and inactivation that is followed by nuclear accumulation of β-catenin, that probably lead to the up-regulation of neuroprotective genes. Our results propose GSK3β as new target for neuroprotection, therefore, we verified that the two GSK3β inhibitors N-(3-Chloro-4-methylphenyl)-5-(4-nitrophenyl)-1,3,4-oxadiazol-2-amine (TC-G 24) and LiCl are neuroprotective agents in OGD and also can be used as PostC agents.
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Although the recognition of facial expressions seems automatic and effortless, discrimination of expressions can still be error prone. Common errors are often due to visual similarities between some expressions (e.g., fear and surprise). However, little is known about the neural mechanisms underlying such a confusion effect. ⋯ No difference between high confusion and low confusion conditions was observed on the M170 component in either the FFA or the pSTS, whilst a difference between two conditions started to emerge in the late positive potential (LPP), with the low confusion condition eliciting a larger LPP amplitude in the FFA. In addition, the power of delta was stronger in the time window of LPP component. This confusion effect was reflected in the FFA, which might be associated with the perceptual-to-conceptual shift.
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Parkinson's disease (PD) is caused by neurodegeneration of nigrostriatal neurons, resulting in dopamine (DA) stimulated motor deficits. Like brain derived neurotrophic factor (BDNF), 7,8-dihydroxyflavone (DHF) is an agonist of the tropomyosin receptor kinase-B (TrkB) and stimulates the same secondary cascades that promote neuronal growth, survival and differentiation. We used our progressive mouse model of PD by administering increasing doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) over 4 weeks (5 days/week), and then treated mice with DHF for 4 weeks after the cessation of the toxin injections (i.e., restoration). ⋯ Expression of the sprouting biomarker, superior cervical ganglion 10 (SCG10), was increased ∼20% in the DL striatum and 66% in the SN/midbrain in mice treated with DHF compared to the MPTP only group. We report that after 4 weeks of progressive MPTP administration, DHF can restore motor deficits and TH within the DL striatum in a TrkB-dependent manner. Our data suggests that DHF may help alleviate motor symptoms of PD and restore the loss of DA terminals within the striatum.
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The cerebellum is involved in the coordination of movement. Its cellular composition is dominated by GABAergic neuronal types, and glial cells are known to express functional receptors. GABAergic signaling regulates cell proliferation, differentiation, and migration during neurodevelopment. ⋯ The second population showed an outward-rectifying current-voltage relationship and responded to muscimol, but dye coupling was absent. These cells received synaptic input and were NG2+, but evoked calcium waves failed to modulate the frequency of spontaneous postsynaptic currents (sPSCs) or signaling into NG2 glia. We conclude that GABAA receptor-mediated signaling is selective for NG2 glia in the WM of the cerebellum.
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Sleep loss or insomnia is among the contributing factors of cognitive deficit, the underlying mechanisms of which remain largely elusive. The endocannabinoid (eCB) system plays a role in sleep, while it is unknown if it is involved in the regulation of memory retrieval by sleep deprivation. In addition, it still controversial how rapid-eye-movement sleep deprivation (REMSD) affects the spatial memory of adolescent mice. ⋯ Mechanistically, REMSD induced eCB-mediated short-term and long-term synaptic plasticity changing including depolarization-induced suppression of inhibition (DSI) in the pyramidal neurons of the hippocampus, in which long-term synaptic plasticity changing was rescued by NESS0327. REMSD downregulated monoacylglycerol lipase, a hydrolase for the endocannabinoid 2-arachidonoylglycerol (2-AG), suggesting the involvement of eCB accumulation and the consequent synaptic plasticity in REMSD-elicited memory impairment in adolescent mice. These findings shed light on the role of sleep disorders in learning and memory deficit of adolescents.