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Melanin-concentrating hormone does not modulate serotonin release in primary cultures of fetal raphe nucleus neurons.
Neuropeptides 2019; 74:70-81N

Abstract

Melanin-concentrating hormone (MCH) is a neuropeptide present in neurons located in the hypothalamus that densely innervate serotonergic cells in the dorsal raphe nucleus (DRN). MCH administration into the DRN induces a depressive-like effect through a serotonergic mechanism. To further understand the interaction between MCH and serotonin, we used primary cultured serotonergic neurons to evaluate the effect of MCH on serotonergic release and metabolism by HPLC-ED measurement of serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels. We confirmed the presence of serotonergic neurons in the E14 rat rhombencephalon by immunohistochemistry and showed for the first time evidence of MCHergic fibers reaching the area. Cultures obtained from rhombencephalic tissue presented 2.2 ± 0.7% of serotonergic and 48.9 ± 5.4% of GABAergic neurons. Despite the low concentration of serotonergic neurons, we were able to measure basal cellular and extracellular levels of 5-HT and 5-HIAA without the addition of any serotonergic-enhancer drug. As expected, 5-HT release was calcium-dependent and induced by depolarization. 5-HT extracellular levels were significantly increased by incubation with serotonin reuptake inhibitors (citalopram and nortriptyline) and a monoamine-oxidase inhibitor (clorgyline), and were not significantly modified by a 5-HT1A autoreceptor agonist (8-OHDPAT). Even though serotonergic cells responded as expected to these pharmacological treatments, MCH did not induce significant modifications of 5-HT and 5-HIAA extracellular levels in the cultures. Despite this unexpected result, we consider that assessment of 5-HT and 5-HIAA levels in primary serotonergic cultures may be an adequate approach to study the effect of other drugs and modulators on serotonin release, uptake and turnover.

Authors+Show Affiliations

Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. Electronic address: gisellefprunell@gmail.com.Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Electronic address: plagos@fmed.edu.uy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30642579

Citation

Saiz-Bianco, Eugenia, et al. "Melanin-concentrating Hormone Does Not Modulate Serotonin Release in Primary Cultures of Fetal Raphe Nucleus Neurons." Neuropeptides, vol. 74, 2019, pp. 70-81.
Saiz-Bianco E, Urbanavicius J, Prunell G, et al. Melanin-concentrating hormone does not modulate serotonin release in primary cultures of fetal raphe nucleus neurons. Neuropeptides. 2019;74:70-81.
Saiz-Bianco, E., Urbanavicius, J., Prunell, G., & Lagos, P. (2019). Melanin-concentrating hormone does not modulate serotonin release in primary cultures of fetal raphe nucleus neurons. Neuropeptides, 74, pp. 70-81. doi:10.1016/j.npep.2018.12.005.
Saiz-Bianco E, et al. Melanin-concentrating Hormone Does Not Modulate Serotonin Release in Primary Cultures of Fetal Raphe Nucleus Neurons. Neuropeptides. 2019;74:70-81. PubMed PMID: 30642579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melanin-concentrating hormone does not modulate serotonin release in primary cultures of fetal raphe nucleus neurons. AU - Saiz-Bianco,Eugenia, AU - Urbanavicius,Jessika, AU - Prunell,Giselle, AU - Lagos,Patricia, Y1 - 2019/01/03/ PY - 2018/09/18/received PY - 2018/12/03/revised PY - 2018/12/30/accepted PY - 2019/1/16/pubmed PY - 2019/4/16/medline PY - 2019/1/16/entrez KW - Cultured serotonergic neurons KW - Embryonic rhombencephalon KW - Melanin-concentrating hormone KW - Serotonergic metabolism SP - 70 EP - 81 JF - Neuropeptides JO - Neuropeptides VL - 74 N2 - Melanin-concentrating hormone (MCH) is a neuropeptide present in neurons located in the hypothalamus that densely innervate serotonergic cells in the dorsal raphe nucleus (DRN). MCH administration into the DRN induces a depressive-like effect through a serotonergic mechanism. To further understand the interaction between MCH and serotonin, we used primary cultured serotonergic neurons to evaluate the effect of MCH on serotonergic release and metabolism by HPLC-ED measurement of serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels. We confirmed the presence of serotonergic neurons in the E14 rat rhombencephalon by immunohistochemistry and showed for the first time evidence of MCHergic fibers reaching the area. Cultures obtained from rhombencephalic tissue presented 2.2 ± 0.7% of serotonergic and 48.9 ± 5.4% of GABAergic neurons. Despite the low concentration of serotonergic neurons, we were able to measure basal cellular and extracellular levels of 5-HT and 5-HIAA without the addition of any serotonergic-enhancer drug. As expected, 5-HT release was calcium-dependent and induced by depolarization. 5-HT extracellular levels were significantly increased by incubation with serotonin reuptake inhibitors (citalopram and nortriptyline) and a monoamine-oxidase inhibitor (clorgyline), and were not significantly modified by a 5-HT1A autoreceptor agonist (8-OHDPAT). Even though serotonergic cells responded as expected to these pharmacological treatments, MCH did not induce significant modifications of 5-HT and 5-HIAA extracellular levels in the cultures. Despite this unexpected result, we consider that assessment of 5-HT and 5-HIAA levels in primary serotonergic cultures may be an adequate approach to study the effect of other drugs and modulators on serotonin release, uptake and turnover. SN - 1532-2785 UR - https://www.unboundmedicine.com/medline/citation/30642579/Melanin-concentrating_hormone_does_not_modulate_serotonin_release_in_primary_cultures_of_fetal_raphe_nucleus_neurons L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4179(18)30169-0 DB - PRIME DP - Unbound Medicine ER -