Effects of lack of microRNA-34 on the neural circuitry underlying the stress response and anxiety

NEUROPHARMACOLOGY

卷:107

Article

Andolina, Diego^1,2,3,4  Di Segni, Matteo^1,2,3  Bisicchia, Elisa¹  D'Alessandro, Francesca^6,7  Cestari, Vincenzo^2,3,7  Ventura, Andrea⁵  Concepcion, Carla⁵  Puglisi-Allegra, Stefano^1,2,3  Ventura, Rossella^1,2,3 

[1] Santa Lucia Fdn, Via Fosso di Fiorano 64, I-00143 Rome, Italy

[2] Sapienza Univ, Dept Psychol, Rome, Italy

[3] Sapienza Univ, Ctr Daniel Bovet, Rome, Italy

[4] Univ Aquila, Dept Appl Clin Sci & Biotechnol, Coppito, Italy

[5] Mem Sloan Kettering Canc, Canc Biol & Genet Program, New York, NY USA

[6] Libera Univ Maria SS Assunta, Dept Human Sci, Borgo St Angelo 13, I-00193 Rome, Italy

[7] Cell Biol & Neurobiol Inst CNR, Via Fosso di Fiorano 64, I-00143 Rome, Italy

关键词: miR-34;    Stress;    Prefrontal cortex;    Amygdala;    Anxiety;   

DOI  :  10.1016/j.neuropharm.2016.03.044

来源: Elsevier

【 摘 要 】

Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters, a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to stress elicits anxiety-like behavior and dendritic remodeling in the amygdala. Members of the miR-34 family have been suggested to regulate synaptic plasticity and neurotransmission processes, which mediate stress-related disorders. Using mice that harbored targeted deletions of all 3 members of the miR-34-family (miR-34-TKO), we evaluated acute stress-induced basolateral amygdala (BLA)-GABAergic and medial prefrontal cortex (mpFC) aminergic outflow by intracerebral in vivo microdialysis. Moreover, we also examined fear conditioning/extinction, stress-induced anxiety, and dendritic remodeling in the BLA of stress-exposed TKO mice. We found that TKO mice showed resilience to stress-induced anxiety and facilitation in fear extinction. Accordingly, no significant increase was evident in aminergic prefrontal or amygdala GABA release, and no significant acute stress-induced amygdalar dendritic remodeling was observed in TKO mice. Differential GRM7, 5-HT2C, and CRFR1 mRNA expression was noted in the mpFC and BLA between TKO and WT mice. Our data demonstrate that the miR-34 has a critical function in regulating the behavioral and neurochemical response to acute stress and in inducing stress-related amygdala neuroplasticity. (C) 2016 The Authors. Published by Elsevier Ltd.

【 授权许可】

Free