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Gene & Protein in Disease Orexin in depression

describes powerlessness that originates from an individual homeostasis and sleep–wake cycles. The autonomic nerve
experiencing events or situations beyond their control. system, reward system, and sleep–wake state are closely,
Reportedly, an animal model of AH depression was used anatomically, and functionally related to the orexin system.
to distinguish rats with AH behavior (AH rats) from The autonomic nervous system, reward system, and
those without AH behavior (No-AH rats). The number emotion regulation may be influenced by the physiological
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of orexin-containing neurons in the hypothalamus was functions of OX1R, according to pharmacological studies
compared among AH, No-AH, and control rats. The using selective antagonists. In one study, mice were tested
concentrations of OXA/OXB peptide, OX1R, and OX2R through a comprehensive suite of behavioral tests to screen
in the brain regions associated with severe depression for additional functions of OX1R; the findings indicated
and those of OXA and corticosterone in the serum that besides its involvement in regulating mood and
were quantified and compared. Higher serum OXA anxiety, OX1R influences social behavior and sensorimotor
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concentrations were observed in AH and No-AH rats gating. 61
than in the control rats. When AH and No-AH rats were Moreover, the relationship between orexin and the
compared, the No-AH rats showed higher brain OXA HPA axis is particularly interesting. Dysregulation of the
levels and more OXA neurons and activity. The number HPA axis is a hallmark of depression, and orexin influences
of OXB neurons and their activity were higher in AH rats. the HPA axis activity (Figure 5). In animal models, chronic
In AH and No-AH rats, orexin receptors and peptides treatment with orexin receptor antagonists alleviated
exhibited distinct patterns in the brain regions pertaining depressive-like behaviors and restored the normal HPA
to severe depression. OXA and OXB play different roles in axis function, indicating a potential therapeutic pathway
AH behavior, and OXA neuron activity may foster resilient for managing depression. 23,62
behavior under stress. 58
Food intake is regulated by the CNS through detection,
The pathophysiology of depression is related to reduced integration, and reaction to numerous internal and external
OXA levels in the CNS, and exogenous treatment of OXA cues. Eating behavior is significantly affected by hedonic
can improve antidepressant effects. However, the processes and reward-related factors. Type 2 diabetes mellitus and
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that underlie these effects remain uncertain. A recent report insulin resistance are related to depression; however, the
indicates that the impact of OXA was related to the activation molecular processes underlying this clinical relationship
of tyrosine receptor kinase B (TrkB) and OX1R in the remain unclear. Orexin controls glucose homeostasis and
ventromedial prefrontal cortex (vmPFC), a neurobiological energy levels, which has been associated with endogenous
hub associated with depression. To analyze the involvement antidepressant processes. Mice with chronic social failure
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of TrkB and OX1R in the behavioral effects exerted by anxiety were administered an orexin-deficient diet,
OXA, rats were injected with 10, 50, and 100 pmol/0.2 μL of and their social behavior and glucose metabolism were
OXA into the vmPFC for the FST and open field test. OXA examined to assess whether orexin is involved in social
signaling in the vmPFC induced OX1R and Trk receptor- behavior and metabolic regulation. Calorie restriction
dependent antidepressive-like effects in the FST. 59
potently activates orexin neurons and may stop the
The mechanisms and key locations of the integration persistence of behaviors resembling depression, thereby
of OXA signaling and photocycle are poorly defined. improving impaired glucose metabolism after prolonged
One study explored the effects of OXA on melatonin stress. Therefore, the orexin system is crucial for preventing
concentrations in the cerebrospinal fluid and plasma at the worsening of the relationship between depression and
night in sheep, wherein the expression of OX1R in the type 2 diabetes. 64
pineal gland was examined during short and long days. Eating disorders are a common component of
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The results implied that day length and nonoptical cues several psychiatric illnesses; however, there is limited
through hypothalamic OXA regulate the endocrine activity understanding of the neurobiology underlying the
of the pineal gland in sheep; this finding has considerable behavioral modifications induced by temporary calorie
ramifications for our comprehension of the circadian clock restriction. At present, rodent forms of depression
functioning and processes by which seasonal animals adjust considerable respond to a 10-day calorie restriction, and
to their environment. Because OXA and melatonin play a this impact is orexin-dependent. After calorie restriction,
role in regulating the sleep–wake system, the findings have the wild-type mice exhibited longer immobility latency
applications in disorders of the human circadian rhythm, and lower complete immobility in FST. Calorie restriction
including jet lag, sleeplessness, and seasonal depression. corrected the behavioral abnormalities in wild-type
OXA and OXB are involved in controlling various mice but not in orexin-mutant animals in a social defeat
behaviors and homeostasis aspects, including energy paradigm of chronic stress. Furthermore, chronic social

Volume 4 Issue 2 (2025) 9 doi: 10.36922/gpd.4210