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.

Walking the Tightrope: A Proposed Model of Chronic Pain and Stress

“…Costing over 300 billion dollars annually (Mucci et al, 2016), chronic stress is categorized as a "worldwide epidemic" by the World Health Organization, and has been associated with increased rates of mental illness and suicide (Rizvi et al, 2017). Although anxiety and stress are similar (Andolina et al, 2016;Ray et al, 2017), psychological stress is less clearly defined than anxiety disorders and as a result, there is not a recognized pharmacological treatment for stress. A review (Shekhar et al, 2005) summarized data supporting the hypotheses that stress induced plasticity within the amygdala may be a critical step in the pathophysiology of the development of chronic anxiety conditions.…”

Amygdalar expression of the microRNA miR‐101a and its target Ezh2 contribute to rodent anxiety‐like behaviour

“…Rodent studies show that acute and chronic stress affect miRNA expression (Meerson et al ., ; Rinaldi et al ., ), and rats that are vulnerable vs. resilient to developing learned helpless behaviour display baseline miRNA expression differences (Smalheiser et al ., ). Several miRNA knockout mice display alterations in anxiety‐like behaviour (Andolina et al ., ; Jin et al ., ). Most work examining behavioural effects of amygdalar miRNA focuses on fear learning (Volk et al ., ).…”

Differential stress induced c-Fos expression and identification of region-specific miRNA-mRNA networks in the dorsal raphe and amygdala of high-responder/low-responder rats

“…Recent findings have demonstrated a causal role for specific miRNAs in mediating stress coping behavior. Mice with miR-17–92 knocked out display increased reactive coping on forced-swim and tail-suspension tests [46], while mice with miR-34 knocked out display resilience to chronic mild stress [47]. However, none of these genetic manipulations have yet to take into account region-specific miRNA expression.…”