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A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission.

Cells (2020-06-05)
Carlos Andrés Lafourcade, Anllely Fernández, Juan Pablo Ramírez, Katherine Corvalán, Miguel Ángel Carrasco, Andrés Iturriaga, Luis Federico Bátiz, Alejandro Luarte, Ursula Wyneken
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Corticosterone, ≥98.5% (HPLC)
Sigma-Aldrich
Trypsin-EDTA solution, 10 ×, sterile-filtered, BioReagent, suitable for cell culture, 5.0 g porcine trypsin and 2 g EDTA, 4Na per liter of 0.9% sodium chloride
Sigma-Aldrich
Anti-GluR1 Antibody, Recombinant, rabbit monoclonal, Upstate®, from rabbit