Venue: Centre Broca
PhD seminars are open to everyone!
Paulo Pinheiro
Principal Investigator, Center for Neuroscience and Cell Biology
Assistant Professor, Department of Life Sciences
University of Coimbra
Paulo Pinheiro was a post-doctoral researcher in Christophe Mulle’s team in 2006-2009.
Title
Chronic stress impacts synaptic transmission and network activity through miR-186-5p
Abstract
Chronic stress has significant negative effects on cognitive and emotional behaviors and is a key risk factor for neuropsychiatric disorders. However, the molecular mechanisms behind these effects remain unclear. Here, we show that chronic stress triggers the upregulation of miR-186-5p, which plays a central role in synaptic dysfunction. Increased miR-186-5p levels were observed in both the prefrontal cortex of stressed mice and neurons exposed to dexamethasone. Overexpression of miR-186-5p in mice induced anxiety- and depressive-like behaviors. This upregulation disrupts the balance between glutamatergic and GABAergic transmission and leads to altered network activity, but can be normalized by a miR-186-5p inhibitor. Our work highlights a new link between chronic stress, miR-186-5p expression, and the synaptic changes underlying behavioral and cognitive dysfunction.
Selected publications
– Rodrigues, B., Leitão, R.A., Santos, M. et al. (2024) “MiR-186-5p inhibition restores synaptic transmission and neuronal network activity in a model of chronic stress”. Molecular Psychiatry
doi.org/10.1038/s41380-024-02715-1– Tawfik B, Martins JS, Houy S, et al. (2021). Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca 2+-dependent priming. Elife. Mar 22;10:e64527. doi: 10.7554/eLife.64527
– Gowrisankaran, S., Steubler, V., Houy, et al. (2020). Endophilin-A controls recruitment, priming and fusion of neurosecretory vesicles. Nature Communications 11(1):1266 doi: 10.1038/s41467-020-14993-8
– Silva M., Rodrigues, B., Fernandes, et al. (2019) MicroRNA-186-5p controls GluA2 surface expression and synaptic scaling in hippocampal neurons. PNAS 116(12):5727-5736. doi: 10.1073/pnas.
1900338116– Vergnano, A. M., Rebola, N., Savtchenko, L. et al. (2014) Zinc Dynamics and Action at Excitatory Synapses. Neuron
82, 1101-1114. DOI: 10.1016/j.neuron.2014.04.034
– Veran, J., Kumar, J., Pinheiro, P. S., et al. (2012) Zinc Potentiates GluK3 Glutamate Receptor Function by Stabilizing the Ligand Binding Domain Dimer Interface. Neuron 76, 565-578. DOI: 10.1016/j.neuron.2012.08.027
– Pinheiro, P. S., Perrais, D., Coussen, F., et al. (2007) GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses. Proceedings of the National Academy of Sciences of the United States of America
104, 12181-12186. DOI: 10.1073/pnas.
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