Franco R Mir1,2,3, Carlos Wilson4,5, Lucas E Cabrera Zapata1, Luis G Aguayo6, María Julia Cambiasso1,7. 1. Laboratorio de Neurofisiología, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina. 2. Cátedra de Fisiología Animal, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina. 3. Cátedra de Fisiología Animal, Departamento de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de La Rioja, La Rioja, Argentina. 4. Laboratorio de Neurobiología, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina. 5. Centro de Investigación en Medicina Traslaciona, Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina. 6. Departamento de Fisiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile. 7. Departamento de Biología Bucal, Facultad de Odontología, Universidad Nacional de Córdoba, Córdoba, Argentina.
Abstract
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.
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.
Authors: Cindy F Yang; Michael C Chiang; Daniel C Gray; Mahalakshmi Prabhakaran; Maricruz Alvarado; Scott A Juntti; Elizabeth K Unger; James A Wells; Nirao M Shah Journal: Cell Date: 2013-05-09 Impact factor: 41.582
Authors: Simon D Harding; Joanna L Sharman; Elena Faccenda; Chris Southan; Adam J Pawson; Sam Ireland; Alasdair J G Gray; Liam Bruce; Stephen P H Alexander; Stephen Anderton; Clare Bryant; Anthony P Davenport; Christian Doerig; Doriano Fabbro; Francesca Levi-Schaffer; Michael Spedding; Jamie A Davies Journal: Nucleic Acids Res Date: 2018-01-04 Impact factor: 16.971
Authors: Franco R Mir; Carlos Wilson; Lucas E Cabrera Zapata; Luis G Aguayo; María Julia Cambiasso Journal: Br J Pharmacol Date: 2020-04-03 Impact factor: 8.739