Page 51 - GPD-4-2

Gene & Protein in Disease Orexin in depression

Figure 7. Relationship between sunlight, orexin, and emotion. Light regulates the suprachiasmatic nucleus through the retina-hypothalamic signaling
pathway and indirectly affects the orexin system by modulating the neurotransmitters and hormones interacting with orexin. Orexin neurons project
to multiple brain regions, regulating mood and cognition by influencing the suprachiasmatic nucleus activity in the circadian rhythm. Altogether, these
mechanisms modulate the monoaminergic system, limbic system, and prefrontal cortex, which are crucial for regulating mood and cognitive processes.
Abbreviations: OX: Orexin system; SCN: Suprachiasmatic nucleus.

excitatory effect on serotonin neurons, whereas high are most likely involved in movement-induced changes
concentrations indirectly inhibit them 103,143 (Figure 4) in the hippocampus. The orexin system may be related
because low orexin concentrations act on its receptors to locomotor behaviour, and a speculative factor that
149
OX1R and OX2R in serotonin neurons, possibly exciting promotes the beneficial effect of exercise is OXA. Similarly,
them by regulating the activity of these receptors; previous research has documented that anorexigenic
91
however, at higher concentrations, orexin may indirectly neurons are closely linked to brain areas implicated in
inhibit serotonin neurons by exciting GABAergic cognitive function and emotional regulation, OXA level
interneurons. 144,145 In another study, adult male rats were increases with exercise, and OXA may affect the synaptic
150
used to induce MIS-related alterations. A subset of these plasticity of hippocampal neurons and hippocampal
rats were treated with CCL for 3 weeks during puberty. neurogenesis by regulating lactate metabolism, thereby
Results demonstrated that CCL therapy affects the affecting cognitive function. Promoting hippocampal
49
serotonin and orexin energy systems in the MIS model neurogenesis is a potential strategy for improving cognitive
but does not affect the reduction of dopamine release in function and treating neuropsychiatric disorders such as
the MIS-induced nucleus accumbens; this observation depression. Hence, the beneficial effect of exercise may
suggests that bright light is associated with improved involve preventing the decline of cognitive function caused
mood and cognitive function. Therefore, restoration of the by degenerating the hippocampus associated with aging, to
orexin system could be associated with the antidepressant improve depressive symptoms.
effects of CCL treatment in cases of depression. 146
Early life stress contributes to the onset of depression. 7. Conclusion
While dealing with stress, orexin neurons drive awakening Depression is a common mental health condition that
and motivational behaviour. Although physical exercise impacts an individual’s well-being and overall health.
147
is widely recognized as a beneficial intervention, the Recent research has highlighted the critical involvement
precise mechanism of action remains incompletely of orexin in the onset and development of depression.
understood. To explore the antidepressant effects of Patients with depression exhibit lower levels of orexin
exercise, researchers have investigated the involvement of than those without depression, along with alterations in
the amygdala, specifically the BLA, in animal models of the expression of orexin receptors. The orexin/receptor
depression. Repeatedly bound mice exhibited depressive system is involved in various functions within the CNS,
behavior, which could be offset by post-stress treatment which is enabled by the extensive projections of orexin-
(exercise). After repeated stress, the hypothalamic secretion containing neurons, complex circuitry involving other
hormone/orexin hormone and MCH were upregulated in neuron types, and widespread distribution of orexin
the BLA, whereas exercise therapy could reduce stress- receptors. Orexin inhibits the release of GABA (Figure 2),
induced depression-like behaviors; these findings indicate which may increase the excitability of orexin neurons
that exercise exerts an antidepressant effect by suppressing that depends on the distinct functions of GABA and
A
the orexin and MCH neural pathways within the BLA. GABA receptors, the distribution of these receptors
148
B
The production of microcirculation and growth factors at presynaptic and postsynaptic locations, and their
Volume 4 Issue 2 (2025) 15 doi: 10.36922/gpd.4210