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Gene & Protein in Disease Orexin in depression

Figure 5. Relationship between orexin and the HPA axis. Orexin can directly bind to the orexin receptor on CRHergic neurons and can influence CRHergic
neurons by binding to the orexin receptors on NEergic or MCH-ergic neurons. When activated by orexin, the level of cAMP in CRHergic neurons
increases, which activates PKA, phosphorylates, and CREB. p-CREB promotes the transcription of the CRH gene, stimulating CRH synthesis and release.
CRH is a key regulator of the HPA axis and can stimulate the anterior pituitary to release ACTH, further facilitating the release of glucocorticoids (such as
cortisol) in the adrenal cortex. Cortisol – a major hormone in stress response – could affect emotional regulation in the brain. Chronic or excessive stress
may cause dysregulation of the HPA axis, which is associated with the onset of depression. (Created using biorender.com).
Abbreviations: ACTH: Adrenocorticotropic hormone; cAMP: Cyclic adenosine monophosphate; CRE: cAMP-response element; CREB: cAMP-response
element-binding protein; CRH: Corticotropin-releasing hormone; HPA: Hypothalamic-pituitary-adrenal; MCH: Melanin-concentrating hormone;
MCHR: Melanin-concentrating hormone receptor; NE: Norepinephrine; NER: Norepinephrine receptor; PKA: Protein kinase A.

(a molecular marker of neuronal activity). The findings electrophysiological studies investigating these cells often
suggested that orexin neurons in the dorsomedial and use postweaning rodents. 24,25 Nevertheless, the functional
perifornical hypothalamic regions, as well as the MCH-ergic maturity these neurons at this time remains unclear.
systems, play a role in the onset of depressive disorders. Studies on the electrical characteristics of MCH neurons
23
MCH and orexin neurons support each other in numerous and orexin in brain slices obtained from postweaning rats
physiological processes, including energy balance and suggested that orexin neurons, after receiving sufficient
the circadian rhythm of sleep and wakefulness. In vitro stimulation before puberty, can generate action potentials

Volume 4 Issue 2 (2025) 5 doi: 10.36922/gpd.4210