The classical hypothesis of brain sexual differentiation posits that gonadal hormones during the critical perinatal period are responsible for the neurochemical and cytoarchitectonic differences in the brains of males and females. However, in the last 20 years, evidence indicates that sex chromosome genes play a direct role in many sexual differences not attributable to hormonal exposure. GABA is the main inhibitory neurotransmitter in the adult central nervous system, but during development, it exerts trophic actions through the opening of voltage-dependent calcium channels. Previous results from our laboratory indicate that there are sexual differences in the response of GABAA receptors in immature hypothalamic neurons. Male neuronal cultures show a greater number of cells that respond with excitation to GABA compared to female cultures, and similar effects are observed in the magnitude of the response. Surprisingly, these differences are independent of testosterone treatment. Our results suggest a different maturation rate of the GABAergic system between males and females, which is not due to exposure to gonadal hormones during the critical period. It is likely that the different sex chromosome complement of males (XY) and females (XX) can explain these differences. Through transgenic mice (Four Core Genotypes), primary cultures of hypothalamic neurons, calcium imaging, electrophysiology, morphometry, molecular biology, and biochemistry, we study this fascinating stage of ontogenetic development.
COMPETITIVE RESEARCH FUNDS
- 2024 – CONSOLIDAR – Type 1 Secretary of Science and Technology – National University of Córdoba. Title: “Gestational Environmental Enrichment in a Postpartum Depression Model: Physiological and Neurobehavioral Effects in Mothers and Adolescent Offspring” Co-Director of the Project.
- 2024 – Neuroscience Capacity Accelerator for Mental Health (NCAMH) program, International Brain Research Organization (IBRO). Title: “Gestational Enriched Environment in a Postpartum Depression Model”. Co-Director of the Project.
- 2022 – PIC 27/A052 – Consolidation Projects (PIC) for research of the Secretary of Science and Technology of the National University of La Rioja (CICYT). Title: “Effect of Gestational Environmental Enrichment on Maternal Physiology and Behavior” Project Director.
- 2021 – PICT-2021-0719 – Initial Researcher (INVI) National Agency for the Promotion of Science and Technology. Fund for Scientific and Technological Research (FONCYT). Title: “Sexual Differences in Depression and Anxiety in Adolescents: Behavior, Neurobiology, and Therapeutic Action of Psilocybin in a Social Isolation Stress Animal Model”. Project Director.
- 2021 – Educational Grant – Committee for Aid and Education in Neurochemistry (CAEN). Category 1B: Research Supplies for use in the applicant’s home laboratory 2021-2022. International Society for Neurochemistry. Project Title: “Role of Sex Chromosome Complement in the Sexually Dimorphic Response to GABAA Receptor Activation in Hypothalamic Neurons”. Project Director.
PUBLICATIONS (LATEST FIVE YEARS)
- “Parental Enriched Environment: A Look Through Key Temporary Windows” Mir F.R., Renard G., Rivarola M.A. Journal of Neuroendocrinology (2023); https://doi.org/10.1111/jne.13308
- “Sex Differences in Anxiety and Depression: What Can (and Cannot) Preclinical Studies Tell Us?” Mir FR, and Rivarola, MA. Sexes 2022. 3(1), 141-163; https://doi.org/10.3390/sexes3010012.
- “Animal models of postpartum depression revisited” Mir FR, Pollano, A, Rivarola, MA. Psychoneuroendocrinology 2022. Feb;136:105590. doi: 10.1016/j.psyneuen.2021.105590
- “Hyperosmolarity-induced vasopressin expression and intrinsic excitability of supraoptic neurons of adult offspring are changed by early maternal separation” Trujillo V,* Mir FR,* Suárez MM, Vivas, L. Psychoneuroendocrinology 2021 May 23;130:105282. doi: 10.1016/j.psyneuen.2021.105282. *equal contribution
- “Postweaning enriched environment enhances cognitive function and brain-derived neurotrophic factor signaling in the hippocampus in maternally separated rats” Cordier JM, Aguggia JP, Danelon V, Mir FR, Rivarola, MA, Mascó D. Neuroscience. 2021 Jan 15;453:138-147. doi: 10.1016/j.neuroscience.2020.09.058
- “Gonadal hormone-independent sex differences in GABAA receptor activation in rat embryonic hypothalamic neurons” Mir FR, Wilson C, Cabrera Zapata LE, Aguayo LG, Cambiasso MJ. Br J Pharmacol. 2020 Jul;177(13):3075-3090. doi: 10.1111/bph.15037
- “Estradiol-dependent axogenesis and Ngn3 expression are determined by XY sex chromosome complement in hypothalamic neurons” Cisternas CD, Cabrera Zapata LE, Mir FR, Scerbo MJ, Arevalo MA, Garcia-Segura LM, Cambiasso MJ. Sci Rep. 2020 May 19;10(1):8223. doi: 10.1038/s41598-020-65183-x
- Complete and updated list available here.
TEAM
