Mounting clinical and preclinical evidences support the involvement of non-coding RNAs such as microRNAs (miRs) in determining behaviour linked to stress. Here, we investigate, for the first time, the possibility that miR-34 family has a role in mediating the behavioral consequences of exposure to chronic social stress. To do it, by longitudinal study, Wild Type (WT) and miR-34 family knockout mice (TKO) underwent chronic social stress and, subsequently, they were tested for anxiety and depressive-like behaviour. We found that WT mice exhibited increased anxiety-like and social avoidance behavior upon exposure to chronic social stress. Interestingly, in the other hand, TKO mice exhibited resilience only for social interaction behavior. Our recent data demonstrated that miR-34 is expressed with high level and specificity in the DRN and we demonstrated that both the constitutive and conditional deletion of miR- 34 family in the DRN of mice attenuates the serotonergic response to stress. Serotonin (5-HT) is a neurotransmitter system that plays an evolutionarily conserved role in regulating affiliative and antagonistic behaviors and the DRN plays a key role in afferent systems in the modulation of socio affective responses. Within the DRN, 5-HT neurons are modulated by GABAergic activity and it has been demonstrated that this neuronal circuit is critical in mediating social avoidance following CDS. Thus, in a second set of experiments, we verified a potential role of miR-34a in mediating GABAergic control on serotonergic neurons in response to stress. We found that acute stress exposure reduced GABA release in the DRN in control mice and that inhibition of miR-34a in the DRN modified this neurochemical response. Collectively, our results suggest a new regulatory mechanism in which MiR-34a modulates GABAergic neurotransmission on DRN 5-HT neurons under stressfull condition and that such regulation could be critical in mediating social avoidance following exposure to CSD.
MicroRNA-34a as possible mediator for acquisition of Avoidance after Chronic Social Defeat / Papagni, Virginia; Ielpo, D; Mattei, F; Guzzo, Sm; Porcheddu, G; Lo Iacono, L; Viscomi, Mt; Carnevali, L; Marchetti, C; Cifani, C; Ventura, R; Andolina, D. - (2022). (Intervento presentato al convegno European Behavioral Pharmacology Society tenutosi a Roma).
MicroRNA-34a as possible mediator for acquisition of Avoidance after Chronic Social Defeat
Papagni Virginia;Ielpo D;Porcheddu G;Lo Iacono L;Andolina D
2022
Abstract
Mounting clinical and preclinical evidences support the involvement of non-coding RNAs such as microRNAs (miRs) in determining behaviour linked to stress. Here, we investigate, for the first time, the possibility that miR-34 family has a role in mediating the behavioral consequences of exposure to chronic social stress. To do it, by longitudinal study, Wild Type (WT) and miR-34 family knockout mice (TKO) underwent chronic social stress and, subsequently, they were tested for anxiety and depressive-like behaviour. We found that WT mice exhibited increased anxiety-like and social avoidance behavior upon exposure to chronic social stress. Interestingly, in the other hand, TKO mice exhibited resilience only for social interaction behavior. Our recent data demonstrated that miR-34 is expressed with high level and specificity in the DRN and we demonstrated that both the constitutive and conditional deletion of miR- 34 family in the DRN of mice attenuates the serotonergic response to stress. Serotonin (5-HT) is a neurotransmitter system that plays an evolutionarily conserved role in regulating affiliative and antagonistic behaviors and the DRN plays a key role in afferent systems in the modulation of socio affective responses. Within the DRN, 5-HT neurons are modulated by GABAergic activity and it has been demonstrated that this neuronal circuit is critical in mediating social avoidance following CDS. Thus, in a second set of experiments, we verified a potential role of miR-34a in mediating GABAergic control on serotonergic neurons in response to stress. We found that acute stress exposure reduced GABA release in the DRN in control mice and that inhibition of miR-34a in the DRN modified this neurochemical response. Collectively, our results suggest a new regulatory mechanism in which MiR-34a modulates GABAergic neurotransmission on DRN 5-HT neurons under stressfull condition and that such regulation could be critical in mediating social avoidance following exposure to CSD.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
