Neuroscience
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Brain ischaemia, which can cause severe nerve injury, is a global health challenge. Long non-coding RNA (lncRNA) growth-arrest specific 5 (Gas5) has been documented to exert tumour suppressive effects in several cancers. However, its role in cerebrovascular disease still requires further investigation. ⋯ LncRNA Gas5 inhibited miR-21 expression, leading to elevated levels of Pten. In vitro experiments revealed that lncRNA Gas5 depletion and miR-21 elevation resulted in the suppression of neuronal apoptosis, thus promoting neuronal survival via the PI3K/Akt signalling pathway. These findings demonstrate that lncRNA Gas5 increases miR-21 and activates Pten, contributing to the development of ischaemic brain injury, supporting the silencing of lncRNA Gas5 as a possible therapeutic target for the treatment of ischaemic brain injury.
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Defective proprioceptive integration may play a role in the pathophysiology of motor symptoms in Parkinson's disease (PD). Dysfunction related to proprioceptively-evoked postural reactions in PD patients is still a controversial issue, with only a limited number of studies to date and mostly discordant results. The aims of the present study were (1) to determine whether or not the proprioceptive defect in PD underlies postural impairment and (2) whether or not deep brain stimulation of the subthalamic nucleus (STN-DBS) affects proprioceptive integration. ⋯ We found a significant positive effect of STN-DBS on these postural features. Our findings indicate that Parkinson patients, even in the absence of any clinical evidence of instability, falls, or freezing, use proprioceptive information for postural control less efficiently than healthy subjects. Furthermore, STN-DBS was found to improve proprioceptive integration, with positive impacts on postural orientation and balance.
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Evidence suggests the hypothalamic-pituitary-adrenal (HPA) axis is involved in Alcohol Use Disorders (AUDs), which might be mediated by an imbalance of glucocorticoid receptor (GR), GRα and GRβ, activity. GRβ antagonizes the GRα isoform to cause glucocorticoid (GC) resistance. In the present study, we aimed to investigate the effects of chronic continuous free-choice access to ethanol on GR isoform expression in subregions of the mesocorticolimbic reward circuit. ⋯ These data indicate that the expression of GRα and GRβ isoforms are differentially affected by ethanol drinking despite HPA-associated peptides remaining unchanged, at least at the time of tissue harvesting. Moreover, the results suggest that GR changes may stem from ethanol-induced GC-resistance in the NAcsh. These findings confirm a role for stress in high ethanol drinking, with GRα and GRβ implicated as targets for the treatment of AUDs.
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Peripheral nerve injury (PNI) is a common clinical disease that causes the partial loss of segmental exercise and sensory and autonomic nervous function, placing a heavy burden on patients and their families. A previous study confirmed that exendin-4 can effectively improve nerve regeneration and functional recovery after PNI. However, the specific mechanisms by which exendin-4-mediates this repair have not been clarified. ⋯ In vitro, exendin-4 could significantly promote the proliferation and migration of SCs by activating the Jak-STAT pathway, which promoted peripheral nerve regeneration. Our results indicate that exendin-4 promotes SC proliferation, migration and nerve regeneration after PNI by activating the Jak-STAT pathway. Our findings provide a basis and direction for further elucidation of the mechanisms of exendin-4 in the repair of PNI and provide a new way to treat PNI.
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Proximodistal heterogeneity in learning-promoted pathway-specific plasticity at dorsal CA1 synapses.
Contextual learning requires the delivery of AMPA receptors to CA1 synapses in the dorsal hippocampus. However, proximodistal heterogeneity of pathway-specific plasticity remains unclear. Here, we examined the proximodistal heterogeneity in learning-induced plasticity at the CA1 synapses with inputs from the entorhinal cortex layer III (ECIII) or from CA3. ⋯ Moreover, trained rats exhibited higher paired-pulse ratios at ECIII-CA1 synapses of intermediate and distal, but not proximal CA1 neurons, which suggested region-specific presynaptic plasticity. Finally, learning was clearly prevented by the bilateral microinjection of a plasticity blocker in the proximal or intermediate, but not distal CA1 subfields, which suggested functional heterogeneity along the proximodistal axis. Understanding region- and pathway-specific plasticity at dorsal CA1 synapses could aid in controlling encoded memory.