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Artículo

5-HT2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress

Jaggar, Minal; Weisstaub, Noelia V.Icon ; Gingrich, Jay A.; Vaidya, Vidita A.
Fecha de publicación: 12/2017
Editorial: Elsevier Inc
Revista: Neurobiology of Stress
ISSN: 2352-2895
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Inmunología

Resumen

Chronic stress enhances risk for psychiatric disorders, and in animal models is known to evoke depression-like behavior accompanied by perturbed neurohormonal, metabolic, neuroarchitectural and transcriptional changes. Serotonergic neurotransmission, including serotonin2A (5-HT2A) receptors, have been implicated in mediating specific aspects of stress-induced responses. Here we investigated the influence of chronic unpredictable stress (CUS) on depression-like behavior, serum metabolic measures, and gene expression in stress-associated neurocircuitry of the prefrontal cortex (PFC) and hippocampus in 5-HT2A receptor knockout (5-HT2A−/−) and wild-type mice of both sexes. While 5-HT2A−/− male and female mice exhibited a baseline reduced anxiety-like state, this did not alter the onset or severity of behavioral despair during and at the cessation of CUS, indicating that these mice can develop stress-evoked depressive behavior. Analysis of metabolic parameters in serum revealed a CUS-evoked dyslipidemia, which was abrogated in 5-HT2A−/− female mice with a hyperlipidemic baseline phenotype. 5-HT2A−/− male mice in contrast did not exhibit such a baseline shift in their serum lipid profile. Specific stress-responsive genes (Crh, Crhr1, Nr3c1, and Nr3c2), trophic factors (Bdnf, Igf1) and immediate early genes (IEGs) (Arc, Fos, Fosb, Egr1-4) in the PFC and hippocampus were altered in 5-HT2A−/− mice both under baseline and CUS conditions. Our results support a role for the 5-HT2A receptor in specific metabolic and transcriptional, but not behavioral, consequences of CUS, and highlight that the contribution of the 5-HT2A receptor to stress-evoked changes is sexually dimorphic.
Palabras clave: 5-Ht2a&Minus;/&Minus; Mice , Despair , Gene Expression , Hippocampus , Prefrontal Cortex , Sexual Dimorphism
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/48821
DOI: http://dx.doi.org/10.1016/j.ynstr.2017.06.001
URL: https://www.sciencedirect.com/science/article/pii/S2352289517300073
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Jaggar, Minal; Weisstaub, Noelia V.; Gingrich, Jay A.; Vaidya, Vidita A.; 5-HT2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress; Elsevier Inc; Neurobiology of Stress; 7; 12-2017; 89-102
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