title: Effects of lack of microRNA-34 on the neural circuitry underlying the stress response and anxiety.
abstract: 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.
authors.affiliation: Santa Lucia Foundation, Via del Fosso di Fiorano, 64-00143 Rome, Italy; Department of Psychology and Center "Daniel Bovet", Sapienza University, Rome, Italy; Department of Applied Clinical Science and Biotechnology, University of L'Aquila, Coppito, Italy. Electronic address: diego.andolina@uniroma1.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Andolina
authors.affiliation: Santa Lucia Foundation, Via del Fosso di Fiorano, 64-00143 Rome, Italy; Department of Psychology and Center "Daniel Bovet", Sapienza University, Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Di Segni
authors.affiliation: Santa Lucia Foundation, Via del Fosso di Fiorano, 64-00143 Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bisicchia
authors.affiliation: Department of Human Sciences, Libera Università Maria SS. Assunta, Borgo Sant'Angelo, 13-00193 Rome, Italy; Cell Biology and Neurobiology Institute - CNR, Via del Fosso di Fiorano, 64-00143 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: D'Alessandro
authors.affiliation: Department of Psychology and Center "Daniel Bovet", Sapienza University, Rome, Italy; Cell Biology and Neurobiology Institute - CNR, Via del Fosso di Fiorano, 64-00143 Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cestari
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer, New York, NY, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ventura
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer, New York, NY, USA.
authors.forename: Carla
authors.initials: C
authors.lastname: Concepcion
authors.affiliation: Santa Lucia Foundation, Via del Fosso di Fiorano, 64-00143 Rome, Italy; Department of Psychology and Center "Daniel Bovet", Sapienza University, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Puglisi-Allegra
authors.affiliation: Santa Lucia Foundation, Via del Fosso di Fiorano, 64-00143 Rome, Italy; Department of Psychology and Center "Daniel Bovet", Sapienza University, Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Ventura
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology / Q000523:psychology; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009415:Nerve Net / Q000378:metabolism*; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000523:psychology
chemical_list: C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs
keywords: Amygdala; Anxiety; Prefrontal cortex; Stress; miR-34