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Artículo

Gonadal hormone-independent sex differences in GABAA receptor activation in rat embryonic hypothalamic neurons

Mir, Franco RafaelIcon ; Wilson Rodriguez, CarlosIcon ; Cabrera Zapata, Lucas EzequielIcon ; Aguayo, Luis G.; Cambiasso, Maria JuliaIcon
Fecha de publicación: 03/2020
Editorial: Wiley Blackwell Publishing, Inc
Revista: British Journal of Pharmacology
ISSN: 0007-1188
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Neurociencias

Resumen

Background and Purpose: GABAA receptor functions are dependent on subunit composition, and, through their activation, GABA can exert trophic actions in immature neurons. Although several sex differences in GABA-mediated responses are known to be dependent on gonadal hormones, few studies have dealt with sex differences detected before the critical period of brain masculinisation. In this study, we assessed GABAA receptor functionality in sexually segregated neurons before brain hormonal masculinisation. Experimental Approach: Ventromedial hypothalamic neurons were obtained from embryonic day 16 rat brains and grown in vitro for 2 days. Calcium imaging and electrophysiology recordings were carried out to assess GABAA receptor functional parameters. Key Results: GABAA receptor activation elicited calcium entry in immature hypothalamic neurons mainly through L-type voltage-dependent calcium channels. Nifedipine blocked calcium entry more efficiently in male than in female neurons. There were more male than female neurons responding to GABA, and they needed more time to return to resting levels. Pharmacological characterisation revealed that propofol enhanced GABAA-mediated currents and blunted GABA-mediated calcium entry more efficiently in female neurons than in males. Testosterone treatment did not erase such sex differences. These data suggest sex differences in the expression of GABAA receptor subtypes. Conclusion and Implications: GABA-mediated responses are sexually dimorphic even in the absence of gonadal hormone influence, suggesting genetically biased differences. These results highlight the importance of GABAA receptors in hypothalamic neurons even before hormonal masculinisation of the brain.
Palabras clave: GABA , GABAAR COMPOSITION , SEX DIFFERENCES , CALCIUM , ELECTROPHYSIOLOGY
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/140286
URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/bph.15037
DOI: http://dx.doi.org/10.1111/bph.15037
Colecciones
Articulos(INIMEC - CONICET)
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Citación
Mir, Franco Rafael; Wilson Rodriguez, Carlos; Cabrera Zapata, Lucas Ezequiel; Aguayo, Luis G.; Cambiasso, Maria Julia; Gonadal hormone-independent sex differences in GABAA receptor activation in rat embryonic hypothalamic neurons; Wiley Blackwell Publishing, Inc; British Journal of Pharmacology; 177; 13; 3-2020; 3075-3090
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