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Gene & Protein in Disease Orexin in depression

Figure 4. Subsequent effects of orexin neuron inhibition. The straight lines connecting orexin neurons and serotonin neurons indicate that low concentrations
of orexin exert a direct excitatory effect on serotonin neurons, whereas high concentrations indirectly inhibit them. Figure created by author.
Abbreviation: LH: Lateral hypothalamus.

receptor function, animal models, and clinical studies. then expresses OX1R (Figure 2). The central amygdala –
Furthermore, it illustrates the potential mechanisms of the the primary output of the amygdala – is vital for processing
orexin system in the onset and development of depression, emotions. The KCNQ3 gene encodes a voltage-gated
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such as its effects on sleep–wake cycle, reward processing, potassium channel subunit expressed in the brain. The
stress response, and energy balance. Finally, the review PCDH10 gene – protocadherin 10 – is a member of the
evaluates the potential of orexin receptor antagonists as a protocadherin subfamily within the cadherin superfamily.
treatment for depression. KCNQ3 and PCDH10 genes play key roles in nervous
system function, and their mutations or abnormal
2. In vitro studies on the role of orexin in expression may be associated with various neurological
depression disorders. Changes in the expression of KCNQ3 and
Disturbances in orexin production can cause sleep disorders PCDH10 genes can disrupt the normal control of
and depression and affect motor activity. Nevertheless, to the effect of the amygdala on orexinergic neurons by
affecting neuronal excitability, synaptic transmission,
date, specific changes caused by the orexin system are not
reported. In a previous study, corticosterone injections neuropeptide expression, neurodevelopment, and neural
were used to examine orexin neurons and corresponding circuits, potentially overactivating the hypothalamic
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behavioral changes in mice with stress-induced depression; orexin system. Persistent high levels of orexin and
melanin-concentrating hormone (MCH) in the basolateral
reportedly, significant levels of external stress-induced amygdala (BLA) caused by stress, as well as the activation
depression may be functionally associated with increased
orexin neuronal activation. 16 of orexin receptors or MCH receptors in the BLA, have
been linked to disruptions in social interactions and mood-
The hypothalamic neuropeptide orexin is related to the related behaviors. The occurrence of high levels of MCH
pathophysiology and accumulation of mental diseases. is related to the activation of the sympathetic nervous
Empirical data indicate a possible association between system as a result of stress, producing norepinephrine and
depression and orexin. Nonetheless, the exact role of orexin results in the excessive proliferation of melanocyte stem
in depression remains unknown, particularly regarding cells. It may also relate to the activation of the HPA axis
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the underlying neurological system and mechanism. Ji et (Figure 5). A study of neural targets influenced by BLA
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al. found that a direct projection exists from the ventral neurons containing MCH or orexin receptors suggested
pallidum; the structure is becoming increasingly important that BLA neurons play a role in social and emotional
due to its role in reward processing, depression, and stress behaviors modulated by the orexin and MCH receptor
reactions. These data demonstrate that orexin inhibits systems. 22
depressive-like behaviors in rats by directly activating The relationship between depression and MCH-ergic
GABAergic neurons in the ventral pallidum. 17
system or hunger remains unclear. Thus, the impact of
Chronic life stressors can increase the risk of depression, extended treatment with selective serotonin reuptake
often causing imbalances in the body. Prolonged stress inhibitors on orexin and MCH neuronal activity in mice
causes changes in neuronal functioning in particular brain subjected to prolonged mild stress was investigated; this
areas that control sociability and mood-related behaviors. was achieved through dual immunohistochemical labeling
The LH sends orexin fibers to the central amygdala, which of orexin- or MCH-containing neurons and c-Fos protein

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