Synapse最新文献

Chronic constriction injury (CCI) of the sciatic nerve was used to establish neuropathic pain (NP) models in rats. CCI rats were then treated with propofol (Pro) and their paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured. In addition, the expression patterns of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10 were detected. CCI rats treated with propofol were further injected with antagomiR-140-3p to verify the role of miR-140-3p in propofol's analgesic actions. In addition to confirming the relationship between miR-140-3p and JAG1, the expression patterns of JAG1 itself were detected. Propofol-treated CCI rats were also injected with Ad-JAG1 (adenovirus-packaged JAG1 overexpression vector and Ad-NC) to test the role of JAG1 in propofol's analgesic mechanism of action. Finally, the levels of JAG1 and Notch pathway-related proteins were detected RESULTS: Propofol was found to alleviate NP, including thermal hyperalgesia and mechanical pain threshold. Propofol could also ameliorate neuroinflammation by up-regulating the expression of IL-10 and inhibiting the release of TNF-α and IL-1β. Mechanically, propofol enhanced the amount of miR-140-3p in CCI rats via the regulation of JAG1. Down-regulation of miR-140-3p, or up-regulation of JAG1, could reduce the protective effect of propofol against NP. Propofol inhibited the activation of Notch signaling via miR-140-3p/JAG1 to realize its analgesic effect CONCLUSION: Our findings indicated that propofol inhibits inflammatory responses and the Notch signaling pathway via miR-140-3p/JAG1 to alleviate NP. These data provide evidence to support a potential clinical therapy for NP.

Although calyx of Held synapses undergo dramatic changes around the hearing onset, previous in vivo studies suggest that the calyx synapses undergo further post-hearing maturation process. While developmental changes over the hearing onset have been extensively studied, this post-hearing maturation process remained relatively little investigated. Because of post-hearing maturation, previous results from studies around hearing onset and studies of post-hearing calyx synapses are somewhat inconsistent. Here, we characterized the post-hearing maturation of calyx synapses with regard to in vitro electrophysiological properties in rats and mice. We found that parameters for residual glutamate in the cleft during a train, EPSC kinetics, and vesicle pool size became close to a full mature level by P14, but they further matured until P16 in the rats. Consistently, the phasic and slow EPSCs evoked by action potential trains at P16 calyx synapses were not different from those at P18 or P25 under physiological extracellular [Ca²⁺ ]_o (1.2 mM). In contrast, the parameters for residual current and EPSC kinetics displayed drastic changes until P16 in mice, and slow EPSCs during the train further decreased between P16 and P18, suggesting that maturation of calyx synapses progresses at least up to P16 in rats and P18 in mice.

The epileptogenic-prone (FAST) and epileptogenic-resistant (SLOW) rat strains have become a valuable tool for investigating neural plasticity. The strains were generated by breeding the rats that required the fewest amygdala stimulations to elicit a stage-5 convulsive seizure (FAST) and rats requiring the most stimulations (SLOW). Previous studies have shown differences in behavior and amygdala physiology in the two strains. This study examined the dendritic morphology of pyramidal neurons in the brains of adult male and female rats of the two strains. The brains were stained with the Golgi-Cox method and the length and branching from layer III pyramidal cells were measured in parietal cortex (Zilles Par1), medial frontal cortex (Zilles Cg3), and orbitofrontal cortex (Zilles AID) in these two strains of rats. We observed significantly longer dendrites in Cg3 in the FAST group but longer dendrites in the SLOW group in AID and Par1. There was also a sex difference (M > F) in Par1 in both strains. These morphological differences can provide insights into the neurobiological basis of the behavioral differences and suggest that localized changes in the amygdala do not occur independently of changes in other brain regions, and especially prefrontal cortex.