miR-9-5p is involved in the rescue of stress-dependent dendritic shortening of hippocampal pyramidal neurons induced by acute antidepressant treatment with ketamine

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Mingardi , J , La Via , L , Tornese , P , Carini , G , Trontti , K , Seguini , M , Tardito , D , Bono , F , Fiorentini , C , Elia , L , Hovatta , I , Popoli , M , Musazzi , L & Barbon , A 2021 , ' miR-9-5p is involved in the rescue of stress-dependent dendritic shortening of hippocampal pyramidal neurons induced by acute antidepressant treatment with ketamine ' , Neurobiology of stress , vol. 15 , 100381 . https://doi.org/10.1016/j.ynstr.2021.100381

Title: miR-9-5p is involved in the rescue of stress-dependent dendritic shortening of hippocampal pyramidal neurons induced by acute antidepressant treatment with ketamine
Author: Mingardi, Jessica; La Via, Luca; Tornese, Paolo; Carini, Giulia; Trontti, Kalevi; Seguini, Mara; Tardito, Daniela; Bono, Federica; Fiorentini, Chiara; Elia, Leonardo; Hovatta, Iiris; Popoli, Maurizio; Musazzi, Laura; Barbon, Alessandro
Contributor organization: SLEEPWELL Research Program
Department of Psychology and Logopedics
Neuroscience Center
Mind and Matter
Genetics
Date: 2021-11
Language: eng
Number of pages: 16
Belongs to series: Neurobiology of stress
ISSN: 2352-2895
DOI: https://doi.org/10.1016/j.ynstr.2021.100381
URI: http://hdl.handle.net/10138/336335
Abstract: Converging clinical and preclinical evidence demonstrates that depressive phenotypes are associated with synaptic dysfunction and dendritic simplification in cortico-limbic glutamatergic areas. On the other hand, the rapid antidepressant effect of acute ketamine is consistently reported to occur together with the rescue of dendritic atrophy and reduction of spine number induced by chronic stress in the hippocampus and prefrontal cortex of animal models of depression. Nevertheless, the molecular mechanisms underlying these morphological alterations remain largely unknown. Here, we found that miR-9-5p levels were selectively reduced in the hippocampus of rats vulnerable to Chronic Mild Stress (CMS), while acute subanesthetic ketamine restored its levels to basal condition in just 24h; miR-9-5p expression inversely correlated with the anhedonic phenotype. A decrease of miR-9-5p was reproduced in an in vitro model of stress, based on primary hippocampal neurons incubated with the stress hormone corticosterone. In both CMS animals and primary neurons, decreased miR-9-5p levels were associated with dendritic simplification, while treatment with ketamine completely rescued the changes. In vitro modulation of miR-9-5p expression showed a direct role of miR-9-5p in regulating dendritic length and spine density in mature primary hippocampal neurons. Among the putative target genes tested, Rest and Sirt1 were validated as biological targets in primary neuronal cultures. Moreover, in line with miR-9-5p changes, REST protein expression levels were remarkably increased in both CMS vulnerable animals and corticosterone-treated neurons, while ketamine completely abolished this alteration. Finally, the shortening of dendritic length in corticosterone-treated neurons was shown to be partly rescued by miR-9-5p overexpression and dependent on REST protein expression. Overall, our data unveiled the functional role of miR-9-5p in the remodeling of dendritic arbor induced by stress/corticosterone in vulnerable animals and its rescue by acute antidepressant treatment with ketamine.
Subject: miR-9-5p
Stress
CORT
Dendrite morphology
Ketamine
REST
MAJOR DEPRESSIVE DISORDER
DOWN-REGULATION
IN-VIVO
EXPRESSION
SIRT1
MICRORNAS
PROMOTES
VOLUME
GENES
PLASTICITY
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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