Orexin/Hypocretin Modulation of Cholinergic Signaling within the Prefrontal Cortex in Response to an Immune Challenge

Orexin modulates neuroinflammation and cholinergic function in the PFC of female rats. Specifically, downregulation of orexin impairs the appropriate neuroimmune and neurochemical responses in the PFC to an immune challenge. Thus, the well-documented age- and AD-associated reduction of orexin signaling may be linked to BFCS degeneration via neuroinflammatory mechanisms. Hampel, H., et al., Revisiting the Cholinergic Hypothesis in Alzheimer's Disease: Emerging Evidence from Translational and Clinical Research. J Prev Alzheimers Dis, 2019. 6(1): p. 2-15. Hagar, J.M., et al., Upregulation of orexin/hypocretin expression in aged rats: Effects on feeding latency and neurotransmission in the insular cortex. Neuroscience, 2017. 350: p. 124-132. Calva, C.B., H. Fayyaz, and J.R. Fadel, Increased acetylcholine and glutamate efflux in the prefrontal cortex following intranasal orexin-A (hypocretin-1). J Neurochem, 2018. 145(3): p. 232-244.