A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission
Stress is a widespread problem in today’s societies, having important consequences on brain function. Among the plethora of mechanisms involved in the stress response at the molecular level, the role of microRNAs (miRNAs) is beginning to be recognized. The control of gene expression by these noncodi...
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MDPI AG
2020-06-01
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author | Carlos Andrés Lafourcade Anllely Fernández Juan Pablo Ramírez Katherine Corvalán Miguel Ángel Carrasco Andrés Iturriaga Luis Federico Bátiz Alejandro Luarte Ursula Wyneken |
author_facet | Carlos Andrés Lafourcade Anllely Fernández Juan Pablo Ramírez Katherine Corvalán Miguel Ángel Carrasco Andrés Iturriaga Luis Federico Bátiz Alejandro Luarte Ursula Wyneken |
author_sort | Carlos Andrés Lafourcade |
collection | DOAJ |
description | Stress is a widespread problem in today’s societies, having important consequences on brain function. Among the plethora of mechanisms involved in the stress response at the molecular level, the role of microRNAs (miRNAs) is beginning to be recognized. The control of gene expression by these noncoding RNAs makes them essential regulators of neuronal and synaptic physiology, and alterations in their levels have been associated with pathological conditions and mental disorders. In particular, the excitatory (i.e., glutamate-mediated) neurotransmission is importantly affected by stress. Here, we found that loss of miR-26a-5p (miR-26a henceforth) function in primary hippocampal neurons increased the frequency and amplitude of miniature excitatory currents, as well as the expression levels of the excitatory postsynaptic scaffolding protein PSD95. Incubation of primary hippocampal neurons with corticosterone downregulated miR-26a, an effect that mirrored our in vivo results, as miR-26a was downregulated in the hippocampus as well as in blood serum-derived small extracellular vesicles (sEVs) of rats exposed to two different stress paradigms by movement restriction (i.e., stress by restraint in cages or by complete immobilization in bags). Overall, these results suggest that miR-26a may be involved in the generalized stress response and that a stress-induced downregulation of miR-26a could have long-term effects on glutamate neurotransmission. |
first_indexed | 2024-03-10T19:27:39Z |
format | Article |
id | doaj.art-5fb3117f72014a62b91ffbd7cf9fe0cc |
institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-10T19:27:39Z |
publishDate | 2020-06-01 |
publisher | MDPI AG |
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series | Cells |
spelling | doaj.art-5fb3117f72014a62b91ffbd7cf9fe0cc2023-11-20T02:26:18ZengMDPI AGCells2073-44092020-06-0196136410.3390/cells9061364A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory NeurotransmissionCarlos Andrés Lafourcade0Anllely Fernández1Juan Pablo Ramírez2Katherine Corvalán3Miguel Ángel Carrasco4Andrés Iturriaga5Luis Federico Bátiz6Alejandro Luarte7Ursula Wyneken8Centro de Investigación e Innovación Biomédica (CIIB), Facultad de Medicina, Universidad de los Andes, Santiago PC 7620001, ChileCentro de Investigación e Innovación Biomédica (CIIB), Facultad de Medicina, Universidad de los Andes, Santiago PC 7620001, ChileCentro de Investigación e Innovación Biomédica (CIIB), Facultad de Medicina, Universidad de los Andes, Santiago PC 7620001, ChileCentro de Investigación e Innovación Biomédica (CIIB), Facultad de Medicina, Universidad de los Andes, Santiago PC 7620001, ChileFacultad de Ingeniería y Ciencias Aplicadas, Universidad de los Andes, Santiago PC 7620001, ChileInstituto de Salud Poblacional, Facultad de Medicina, Universidad de Chile, Santiago PC 8380453, ChileCentro de Investigación e Innovación Biomédica (CIIB), Facultad de Medicina, Universidad de los Andes, Santiago PC 7620001, ChileBiomedical Neuroscience Institute, Universidad de Chile, Santiago PC 8380453, ChileCentro de Investigación e Innovación Biomédica (CIIB), Facultad de Medicina, Universidad de los Andes, Santiago PC 7620001, ChileStress is a widespread problem in today’s societies, having important consequences on brain function. Among the plethora of mechanisms involved in the stress response at the molecular level, the role of microRNAs (miRNAs) is beginning to be recognized. The control of gene expression by these noncoding RNAs makes them essential regulators of neuronal and synaptic physiology, and alterations in their levels have been associated with pathological conditions and mental disorders. In particular, the excitatory (i.e., glutamate-mediated) neurotransmission is importantly affected by stress. Here, we found that loss of miR-26a-5p (miR-26a henceforth) function in primary hippocampal neurons increased the frequency and amplitude of miniature excitatory currents, as well as the expression levels of the excitatory postsynaptic scaffolding protein PSD95. Incubation of primary hippocampal neurons with corticosterone downregulated miR-26a, an effect that mirrored our in vivo results, as miR-26a was downregulated in the hippocampus as well as in blood serum-derived small extracellular vesicles (sEVs) of rats exposed to two different stress paradigms by movement restriction (i.e., stress by restraint in cages or by complete immobilization in bags). Overall, these results suggest that miR-26a may be involved in the generalized stress response and that a stress-induced downregulation of miR-26a could have long-term effects on glutamate neurotransmission.https://www.mdpi.com/2073-4409/9/6/1364miRNAshippocampal neuronsextracellular vesiclesstresssynapses |
spellingShingle | Carlos Andrés Lafourcade Anllely Fernández Juan Pablo Ramírez Katherine Corvalán Miguel Ángel Carrasco Andrés Iturriaga Luis Federico Bátiz Alejandro Luarte Ursula Wyneken A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission Cells miRNAs hippocampal neurons extracellular vesicles stress synapses |
title | A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission |
title_full | A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission |
title_fullStr | A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission |
title_full_unstemmed | A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission |
title_short | A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission |
title_sort | role for mir 26a in stress a potential sev biomarker and modulator of excitatory neurotransmission |
topic | miRNAs hippocampal neurons extracellular vesicles stress synapses |
url | https://www.mdpi.com/2073-4409/9/6/1364 |
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