{"id":"https://openalex.org/G556943390","display_name":"The role of microglia in mediating the deleterious effects of stress during adolescence","description":"Studies suggest that trauma during adolescence, a critical period of neurodevelopment, acts as a risk factor for the development of psychiatric disorders. Microglia, the resident immune cells of the central nervous system, appear to play an important role in mediating the response to exposure to traumatic events. Microglia activation can have both protective and harmful effects, depending on the context. Recent studies from our lab reveal that exposing male mice to a stress protocol between postnatal days 31 and 40, a period corresponding to adolescence in humans, causes a range of behavioral alterations (anxiety-like responses, cognitive deficits, and reduced sociability) in adulthood. These changes were associated with the negative impact of trauma on parvalbumin (PV)-expressing GABAergic interneurons and the specialized extracellular matrix surrounding them, the perineuronal nets (PNNs), in the ventral hippocampus (vHip). Changes in microglia activity seem to contribute to alterations in the structure of PNNs and, consequently, to the impairment of PV interneurons. However, this has not yet been explored in studies investigating exposure to stressors. Thus, our hypothesis is that trauma exposure during adolescence will affect microglia activity, leading to behavioral deficits and changes in PV and PNN expression. We will assess the short- and long-term effects of trauma during adolescence on microglial activity. Additionally, we will evaluate whether systemic treatment with minocycline, which inhibits increased microglial activity, and PLX5622, a CSFR1 antagonist that depletes microglia, attenuate the impact of adolescent stress on behavior and PV and PNN expression in adulthood. We will also evaluate the effects of the local infusion of clodronate disodium (CDS) in the vHip, which depletes microglia, on the stress-induced changes. Additionally, we will investigate whether prior trauma exposure in adolescence increases microglial responsiveness ('priming') in adulthood when exposed to an agent that enhances microglia activity. Finally, we will evaluate transcriptomic changes in the vHip microglia of animals exposed to adolescent stress, with or without local microglial depletion through CDS infusion. Results from these studies may contribute to a better understanding of the role of microglia in the deleterious effects of adolescent stress and inform potential targets for the prevention and/or treatment of psychiatric disorders in which stress acts as a risk factor. (AU)","funder_award_id":"24/20348-6","funder":{"id":"https://openalex.org/F4320320997","display_name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi":"10.13039/501100001807"},"funded_outputs":["https://openalex.org/W4414000607","https://openalex.org/W7202344630","https://openalex.org/W7214586368"],"funded_outputs_count":3,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":null,"currency":"BRL","amount_usd":null,"amount_usd_basis":null,"recipients":[],"recipient_countries":[],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"grant","funder_scheme":"Aux\u00edlio \u00e0 Pesquisa - Regular","start_date":"2025-06-01","end_date":"2028-05-31","start_year":2025,"end_year":2028,"landing_page_url":"https://bv.fapesp.br/en/processo/24/20348-6","doi":null,"provenance":"fapesp_bv","lead_investigator":{"given_name":"Felipe","family_name":"Villela Gomes","orcid":null,"role_start":null,"affiliation":{"name":"Universidade de S\u00e3o Paulo (USP). Faculdade de Medicina de Ribeir\u00e3o Preto (FMRP)","country":"Brazil","ids":null},"author":null,"institutions":[]},"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G556943390","primary_topic":{"id":"https://openalex.org/T11266","display_name":"Neuroinflammation and Neurodegeneration Mechanisms","score":0.7873,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11266","display_name":"Neuroinflammation and Neurodegeneration Mechanisms","score":0.7873,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"institution_awarded":[{"id":"https://openalex.org/I1331278255","display_name":"Universidade de Ribeir\u00e3o Preto","ror":"https://ror.org/00ey54k21","country_code":"BR","type":"education","lineage":["https://openalex.org/I1331278255"]}],"updated_date":"2026-10-21T03:01:06.000Z","created_date":"2026-07-13T04:22:39.000Z"}