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Gene & Protein in Disease Orexin in depression

areas of the brain. These projections are closely connected sleep/wake regulation, appetite regulation, and depression
with neurons in the locus coeruleus, limbic system, ventral and anxiety research. Inhibition of orexin neurons and a
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dorsal opercular area, and ventrolateral preoptic nucleus, decrease in orexin levels can cause depression; by affecting
among others (Figure 2). These interactions exert various the sleep–wake cycle, these changes can cause narcolepsy
physiological functions. Orexin concentrations increase and result in learning and memory deficits. Low activity
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in certain pathological conditions, such as posttraumatic of the orexin system is also associated with paroxysmal
stress disorder (PTSD), and decrease in other conditions, sleeping sickness. 8
such as memory deficits. 4 The role of orexin in depression potentially stems from
The orexin system is an important regulator for several its pivotal role in regulating arousal and mood through
neural functions and a valuable drug target. Furthermore, complex neurophysiological interactions. By regulating
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orexin neuropeptides have received increasing attention in the neurotransmitter systems, orexin contributes to the
neuroscience research and are applied in numerous fields, neurobiological processes underlying mood disorders,
including reward and motivation, addiction mechanisms, which targets orexin as a potential factor for novel

Figure 1. Amino acid sequence of OXA and OXB in different species. Orexin is distributed in humans, rats, and mice. Among the three species, the amino
acid sequence of OXA was consistent, whereas that of OXB was different. Figure created by author.
Abbreviations: OXA, Orexin-A; OXB, Orexin-B.

Figure 2. Schematic of the role of the orexin system in the central nervous system
Abbreviations: CeA: Central amygdala; CRH: Corticotropin-releasing hormone; DR: dorsal raphe; GABA: Gamma-aminobutyric acid; Glu: Glutamic acid;
LC: Locus coeruleus; LDT: Lateral–dorsal tegmental nucleus; LH: Lateral hypothalamus; LHb: Lateral habenular nucleus; NAc: Nucleus accumbens; PPT:
Pedunculopontine nucleus; TMN: Tuberomammillary nucleus; VLPO: Ventrolateral preoptic area; VTA: Ventral tegmental area.

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