• Molecules and Cells
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• 제45권5호
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• pp.306-316
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• 2022

Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress. These genes were enriched in neuroactive ligand-receptor interaction, the cAMP (cyclic adenosine monophosphate) signaling pathway, circadian entrainment, and synaptic signaling from the Kyoto Encyclopedia of Genes and Genomes pathway analysis and responded to corticosteroids, positive regulation of lipid transport, anterograde trans-synaptic signaling, and chemical synapse transmission from the Gene Ontology analysis. Based on protein-protein interaction network analysis of the DEGs, we identified neuroactive ligand-receptor interactions, circadian entrainment, and cholinergic synapse-related subclusters. Additionally, cell type and habenular regional expression of DEGs, evaluated using a recently published single-cell RNA sequencing study (GSE137478), strongly suggest that DEGs related to neuroactive ligand-receptor interaction and trans-synaptic signaling are highly enriched in medial habenular neurons. Taken together, our findings provide a valuable set of molecular targets that may play important roles in mediating the habenular response to stress and the onset of chronic stress-induced depressive behaviors.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.427-448
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• 2019

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying $K^+$ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.

• Journal of Acupuncture Research
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• 제19권1호
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• pp.159-174
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• 2002

Objective : The meridian theory in oriental medicine explains that each acu-point has a characteristic functional effect. It will be supposed that an acupuncture stimulation on different acu-point evokes different activation on different areas in the central nervous system(CNS) according to the meridian theory. On this supposition, our group tried the semi-quantitative [14C]2-deoxyglucose([14C]2-DG) autoradiography on the acupuncture stimulation to the hindlimb acu-points of Sprague-Dawley rats. Methods : A venous catheter for the intravenous administration of isotope was equipped in the right external jugular vein on 3 days prior to the [14C]2-DG study. On the day of the study, two acupuncture needles were inserted into the ST36(Zusanli) or LR3(Taichong) on the left hindlimb. Electro-acupuncture stimulation (2 Hz, 5 ms, 1~3 mA, 15 minutes) started just before the i.v. injection of [14C]2-DG ($25{\mu}Ci/rat$). The brain and the spinal cord were removed and processed for the [14C] 2-DG autoradiography. Results : The EA stimulation on ST36 reveals over 120% metaboilc activation in Arcuate nucleus, Anterior pretectal nucleus, Dorsal cochlear nucleus, Interposed cerebellar nucleus, and Nucleus of Darkschewitsch. The EA stimulation on LR3 reveals over 120% metaboilc activation in Lateral habenula nucleus, Medial vestibular nucleus, Ventromedial thalamic nucleus, Anteroventral thalamic nucleus, Anterior cingulate cortex, Dentate gyrus, Antero cortical amygdaloid nucleus, Anterior pretectal nucleus, and Dorsal tegmental nucleus compared with the non EA stimulation control group. Conclusion : These results demonstrate that the different acu-points evoke the different activations in brain areas. And with this functional brain mapping study, a new scientific elucidation for the basis of the acupuncture-meridian theory in oriental medicine through differences of activated area in CNS according to the each acupuncture point.