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Gene & Protein in Disease Orexin in depression

through the opening and closing of ion channels. These a role in controlling neuronal excitability and synaptic
action potentials are then transmitted along the axon communication in the central nervous system (CNS).
to the presynaptic terminal, in which they transmit the A study investigating the role of endogenous adenosine in
electrical signal to the next neuron through the release of controlling excitatory glutamatergic synaptic transmission
neurotransmitters. Meanwhile, MCH neurons continue to orexin neurons indicated that endogenous adenosine
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to develop until late puberty. These data provide some within the hypothalamus is released into the extracellular
guidance for judging the onset time of depression. space in an activity-dependent manner, preventing the long-
Orexin-producing hypothalamic neurons communicate term potentiation of orexin neurons and basal excitatory
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their predominantly neuroexcitatory signals throughout synaptic transmission through adenosine A1 receptors.
the brain through extensive axonal projections. A major Caffeine, a nonselective adenosine receptor antagonist,
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noradrenergic nucleus of the brain is the locus coeruleus, exerts stimulating effects on arousal and sympathetic
to which the LH sends abundant orexin connections activity. In sleep-deprived mice, the administration of
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(Figure 2). Neurons in the LH that respond to glucose caffeine resulted in a remarkable increase in spontaneous
levels produce OXA and OXB and project their axons to the activity. In particular, the wake-promoting effects of
hippocampus (Figure 2), where OX1R, primarily sensitive caffeine in sleep-deprived mice were reversed by an orexin
to OXA, is predominantly expressed. The behavior of rats receptor antagonist, indicating that orexin is essential in
was evaluated using the Morris water maze test, and the mediating the pharmacological effects of caffeine. 36
impact of OXA on synaptic transmission at the Schaffer Using whole-cell patch-clamp recordings on acute
collateral/commissural-CA1 pathway in hippocampal sections of the dorsal raphe nucleus (DRN), OXB exerts
slices was investigated, focusing on long-term depression a suppressive effect on glutamate-induced synaptic
and potentiation. The obtained results emphasized the currents within DRN serotonin neurons. In acute mouse
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adverse effects of OXA on spatial cognition, which can be brain slices, glycine – a neurotransmitter known for its
attributed to the suppression of long-term potentiation in involvement in the brainstem and spinal cord – induces
the Schaffer collateral-CA1 hippocampal synapses. 29 dose-dependent postsynaptic Cl currents in orexin cells.
−
Corticotropin-releasing hormone (CRH) and orexin are Pharmacological analysis of glycine receptor responses
involved in modulating excitatory synaptic transmission revealed that although orexin neurons in the early postnatal
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in the ventral cover region. The clinical manifestations period possess the α2-subunit, mature orexin neurons
of depression often include disrupted sleep patterns. CRH possess α/β-heteromeric glycine receptors, implying that
may influence sleep. Neurons from the arcuate nucleus the two pools of glycine receptors control the activity of
that secrete the neuropeptide Y/agouti-related peptide growing orexin cells. 38
and anorexigenic proopiomelanocortin/cocaine- and For obesity or short-term food deprivation, OXA
amphetamine-regulated transcript peptides project to the neurons exhibit increased activity levels, resulting in
LH, regulating orexin-containing neurons, which increase hyperarousal and an increased drive to seek food.
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food intake, and they also project to the paraventricular Although brief exposure to a high-fat diet can cause
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nucleus, regulating CRH neurons to decrease feeding. synaptic plasticity in the mesolimbic pathway, whether
Considering the anatomical and neurophysiological orexin neurons are affected by this modification remains
interactions between orexin and the CRH system, these unclear. Reportedly, the intake of appetizing high-fat diets
two neuropeptides hypothetically interact with each other. can trigger long-lasting synaptic depression in excitatory
To explore this hypothesis, the impact of dysfunction in connections targeting orexin neurons; this finding suggests
the CRH receptor system on the wake-promoting effects the presence of a homeostatic mechanism aimed at
of exogenous orexin was investigated using two different preventing the excessive activation of these neurons and
CRH receptor knockout models; notably, the possible reducing the intake of high-fat diets. A brief exposure to
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action of CRH did not affect the wake-promoting effect a high-fat diet may increase the levels of certain excitatory
of orexin. The epidermal growth factor receptor (EGFR) neurotransmitters in the brain, resulting in prolonged
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controls neural activity in vertebrates and the sleep–wake inhibition of orexin neurons. The neuropeptide orexin,
cycle. Hypothetically, EGFR signaling mediates the orexin synthesized by neurons located in the LH, is associated
system activity during the onset of sleep. 33 with obesity and anxiety-related depression. The protein
Endogenous adenosine, produced by cells within the delta-like homology 1 (DLK1), expressed by every
body, promotes sleep. When ATP is released from inside orexin neuron, may aid in the control of anxiety-related
the cell into the extracellular space and destroyed by ecto- depression and energy balance. DLK1 was concurrently
ATPases, endogenous adenosine is generated. It plays expressed by all rat orexin neurons, which is consistent
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Volume 4 Issue 2 (2025) 6 doi: 10.36922/gpd.4210