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Gene & Protein in Disease Orexin in depression

the combination of equilibrium and kinetics with the cognitive function in mice with chronic kidney disease.
selective OX2R antagonist radioligand [³H]-EMPA The mechanism underlying this effect may involve the
investigated the effects of almorexant. Based on an analysis upregulation of OXA expression and the augmentation
using a hemiequilibrium model, the dissociation of of CaMKKβ/AMPK phosphorylation. These changes
antagonists in a biological system occurs at a slower rate subsequently inhibit the downstream signaling pathway of
than membrane binding. In such scenarios, almorexant nuclear factor-κB, reduce the production of inflammatory
acts as a pseudoirreversible antagonist. 132 cytokines such as interleukin-1β (Figure 3), and reduce
Another study using an animal model of depression inflammation, thereby ameliorating the inflammatory state
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showed that the pharmacological blockage of orexin associated with central and peripheral system disorders
receptors exerts a strong antidepressant-like effect. The and further affecting the onset, development, and
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effect of intracerebral venous administration of OXA on treatment of depression. Exogenous OXA administration
FST and cell proliferation with bromodeoxyuridine (BrdU) substantially improved lung histology and reduced
in the dentate gyrus was investigated in another study. inflammation levels, emphasizing the importance of
BrdU was used to label and quantify newborn neurons in neuroimmune interaction and suggesting that OXA holds
the hippocampus. OXA administration notably reduced promise as a therapeutic agent for acute lung injury. 140
the immobility of animals in the FST without affecting The development and occurrence of psychosis are closely
spontaneous motor activity or serum cortical ketone associated with the functional modulation of the orexin
levels. Moreover, the number of BrdU-positive cells in the system in the CNS. Depression and physical symptoms
dentate gyrus substantially increased in OXA-treated mice. are linked to abnormal alterations in the hypothalamic
Treatment with the OX1R antagonist SB334867 blocked lateral region. The pathophysiology of depression may
the OXA-induced decrease in immobility in the FST and be revealed through traditional Chinese medication
the increase in BrdU positivity; these findings show that Xiaoyaosan that controls these alterations. A depressed
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OXA exerted an antidepressant effect. rat model was established to observe the changes in the
Although preclinical studies on orexin receptor OXA/OX1R expression in the LH and the intervention
antagonists indicate antidepressant effects, a remarkable of Xiaoyaosan; Xiaoyaosan could considerably reverse
limitation is the reliance on short-term animal models, the expression of OXA/OX1R in the LH, and the curative
which may not completely capture the chronic nature effect was remarkable. The pathophysiology of depression
of depression. Longitudinal studies incorporating long- and somatic symptoms is intimately pertaining to the
term or chronic intervention models are required to gain aberrant alterations of OXA/OX1R in the LH of depressed
clinically relevant insights. rats induced by prolonged stress. By controlling OXA/
OX1R, Xiaoyaosan could alleviate physical complaints and
Pharmacological evidence suggests a link between depression. 141
the orexin, monoamine, and cannabinoid systems in
appetite and emotional behavior control. The orexin Light intensely affects the behavior and physiology of
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and endocannabinoid systems exhibit numerous shared almost all animals, including humans. Reportedly, exposure
biological functions, encompassing arousal, stress response, to relatively dim light throughout the day was associated
mood regulation, and reward processing. Reportedly, with increased depression- and anxiety-like behaviors
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OXA may activate postsynaptic OX1R and induce and impaired spatial memory. In contrast, bright light
2-AG production, a mechanism achieved through the during the day reduced depressive and anxious behaviors
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Gq-protein-mediated PLC-DAGL enzyme cascade. The along with improving spatial memory. Orexin is a vital
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activation of G-proteins activates downstream signaling mediator of these effects because it responds to changes in
pathways, suggesting that the orexin/receptor system can light levels during the day and transmits this information
activate effective intracellular signaling through these to other brain regions associated with emotional behavior
signaling pathways (Figure 3). and spatial memory (Figure 7).
Chaihu-Jia-Longgu-Muli decoction (CLMD) is an Maternal and infant separation (MIS) is a mature
ancient prescription documented in the Treatise on Febrile depression model. Reportedly, chronic continuous light
Diseases by Zhang Zhongjing, the renowned figure in (CCL) treatment during puberty can effectively mitigate
traditional Chinese medicine. CLMD has been widely depression-like behavior triggered by MIS. Long-term
used and has demonstrated its efficacy in ameliorating light altered the serotonin and orexin system in the brain
chronic inflammatory condition in mice with chronic of rats. The speculation from such studies is that a certain
kidney disease. Evidently, CLMD intervention may relationship exists between serotonin and orexin system
regulate energy metabolism and improve sleep quality and in depression. Low concentrations of orexin exert a direct

Volume 4 Issue 2 (2025) 14 doi: 10.36922/gpd.4210