MicroRNA-mediated control of synaptic transmission in chronic stress

Host

Nicolas Gutierrez (PhD), Ana Rita Mendes (MSc) and Inês Dias (MSc), Neuroethology Lab

Venue

Seminar room

Abstract

Chronic stress exerts profound negative effects on cognitive and emotional behaviours and is a major risk factor for the development of neuropsychiatric disorders. However, the molecular links between chronic stress and its deleterious effects on neuronal and synaptic function remain elusive. We found that miR-186-5p, an activity-regulated microRNA that regulates excitatory transmission, is upregulated by chronic stress and may be a key mediator of such changes, leading to synaptic dysfunction. Our results show that the expression levels of miR-186-5p are increased in the prefrontal cortex (PFC) of mice exposed to chronic stress and of major depressive disorder patients. Additionally, viral overexpression of miR-186-5p in the PFC of naïve mice induces anxiety- and depressive-like behaviours. The upregulation of miR-186-5p through prolonged glucocorticoid receptor activation in vitro, or in a mouse model of chronic stress, causes an imbalance in excitation/inhibition that leads to altered neuronal network activity, which could be rescued by a miR-186-5p inhibitor. Overall, our results establish a novel molecular link between chronic glucocorticoid receptor activation, the upregulation of miR-186-5p and the synaptic changes induced by chronic stress, that may be amenable to therapeutic intervention.

Biography

Ana Luisa Carvalho is an Associate Professor at the Department of Life Sciences and a group leader at the CNC-Center for Neuroscience and Cell Biology, University of Coimbra. Additionally, she holds the position of Vice-President at CNC and coordinates the Neuroscience and Disease Thematic Line at the Associate Laboratory CIBB-Center for Innovative Biomedicine and Biotechnology. She trained in Neuroscience during her PhD under the mentorship of Carlos B Duarte (University of Coimbra) and Richard Huganir (Johns Hopkins University, USA), and later during her postdoctoral work guided by Ann Marie Craig (University of British Columbia, Canada). Her research delves into cellular and molecular mechanisms governing neuronal excitability and synaptic function, with a focus on their implications in brain diseases. Noteworthy contributions include identifying receptor/channel-associated proteins and metabolic hormones regulating synaptic function and plasticity, and crucial insights into synaptic dysfunction in brain disorders. As a mentor, she has guided 20 PhD and 19 MSc students, and she coordinated the MSCA-ITN European Training Network Syn2Psy, focused on Synaptic Dysfunction in Neuropsychiatric Disorders. She is presently Vice-President of the Cajal Advanced Neuroscience Training Program.

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Champalimaud Research (CR) Colloquia Series is a seminar programme organised by the Champalimaud Centre for the Unknown to promote the discussion about the most interesting and significant questions in neuroscience and physiology & cancer with appointed speakers by the CR Community.