Neuroscience
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Post-traumatic stress disorder (PTSD) patients exhibit abnormal learning and memory. Axons from orexin neurons in the lateral hypothalamus innervate the hippocampus, modulating learning and memory via the orexin 1 and 2 receptors (OX1R and OX2R). However, the role of the orexin system in the learning and memory dysfunction observed in PTSD is unknown. ⋯ The results showed that spatial memory was impaired and food intake was decreased in SPS rats; this was accompanied by downregulation of orexin-A in the hypothalamus and upregulation of OX1R and OX2R in the hippocampus and of OX1R in the hypothalamus. Intracerebroventricular administration of orexin-A improved spatial memory and enhanced appetite in SPS rats and partly reversed the increases in OX1R and OX2R levels in the hippocampus and hypothalamus. These results suggest that the orexin system plays a critical role in the memory and appetite dysfunction observed in PTSD.
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The NOD-like receptor family Pyrin domain-containing 3 (NLRP3) inflammasome has a crucial role in the inflammatory process that occurs during intracerebral hemorrhage (ICH)-induced injury. Histone deacetylase 10 (HDAC10) is a newly identified class II histone deacetylase involved in immune responses. However, how HDAC10 affects the inflammatory response after ICH remains unknown. ⋯ Furthermore, HDAC10 silencing also promoted the interaction of PTPN22 and NLRP3. Our study demonstrated that HDAC10 silencing aggravated NLRP3-mediated inflammatory responses after ICH in rats via the PTPN22 pathway. These results suggest that regulating the NLRP3 inflammasome may be a novel method to ameliorate ICH injury.
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Zinc is a trace element that is essential for a large number of biological and biochemical processes in the body. In the nervous system zinc is packaged into synaptic vesicles by the ZnT3 transporter, and synaptic release of zinc can influence the activity of postsynaptic cells, either directly through its own cognate receptors, or indirectly by modulating activation of receptors for other neurotransmitters. Here, we explore the anatomical and functional aspects of zinc in the circadian system. ⋯ Finally, entrainment, free-running, and circadian responses to light were explored in mice lacking the ZnT3 gene. In every aspect explored, the ZnT3 knockout mice were not significantly different from their wildtype counterparts. These findings highlight the presence of zinc in areas critical for circadian functioning but have yet to identify a role for zinc in these areas.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron loss and gliosis in the spinal cord, brain stem and cortex. The Notch signaling pathway has been reported to be dysfunctional in neurodegenerative diseases, including ALS. However, the exact mechanism is still unclear. ⋯ We found that Notch activation was universal in proliferating astrocytes and that the Notch ligand Jagged1 was uniquely upregulated in proliferating microglia, while DLL4 expression was increased in both activated astrocytes and degenerating oligodendrocytes. Our results indicate that microglia may play an important role in the intercellular receptor-ligand interaction of the Notch signaling pathway and contribute to the pathogenesis of motor neuron loss in ALS mice. Further experiments are required to clarify the exact mechanism responsible for Notch dysfunction in ALS.
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Tuning of the cardiovascular response is crucial to maintain performance during high-intensity exercise. It is well known that the nucleus of the solitary tract (NTS) in the brainstem medulla plays a central role in cardiovascular regulation; however, where and how upper brain regions form circuits with NTS and coordinately control cardiovascular responses during high-intensity exercise remain unclear. Here focusing on the amygdala and claustrum, we investigated part of the mechanism for regulation of the cardiovascular system during exercise. ⋯ Simultaneous stimulation of the central nucleus of the amygdala and pCL showed a greater pressor response compared with the stimulation of the amygdala alone. These results suggest the amygdala and pCL are involved in different phases of exercise. More speculatively, these areas might coordinately tune cardiovascular responses that help maintain performance during high-intensity exercise.