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  • br Material and methods br Results

    2021-10-23


    Material and methods
    Results
    Discussion Accumulating evidence suggests that the hippocampus is sensitive to noise-induced hearing loss and other forms of sensory deprivation, which deprives the hippocampus of sensory information required for its normal operations such as spatial navigation and memory formation (Smith et al., 2005a, 2005b; Cui et al., 2009; Cheng et al., 2011). Previous studies have shown that noise-induced hearing loss can suppress cell proliferation and neurogenesis in the hippocampus (Kraus et al., 2010; Newman et al., 2015). Because increased stress and elevated stress hormone levels can suppress neurogenesis, we investigated whether noise-induced hearing loss may serve as a stressor and alter basal corticosterone levels, reactive corticosterone levels and/or the endothelin receptor levels of GRs and MRs in the dentate gyrus of the hippocampus.
    Conflicts of interest
    Acknowledgements This work was supported in part by National Institutes of Health grants 5R01DC011808, R01DC014452, and R01DC014693. The authors would like to thank Dr. Kelly Radziwon and Dr. Gail Seigel for their helpful comments on earlier versions of the manuscript.
    Introduction Major depressive disorder (MDD) is a common neuropsychiatric disorder that affects approximately 300 million people worldwide [1]. Depression is mainly manifested as depressed mood, retardation of thought, loss of interest and enjoyment, and decline of cognitive function. It could even lead to suicide in some patients, bringing a heavy burden to patients, families and society. Stress event is an important factor for depression [2]. Most individuals recover to normal state after stress, while some develop into depression. The pathogenesis of susceptibility or resilience remains unclear [[3], [4], [5], [6]]. The hypothalamic-pituitary-adrenal (HPA) axis is activated upon stress. Stress hormones such as glucocorticoid (cortisol in humans, corticosterone (CORT) in rodents) are secreted by the adrenal cortex. Glucocorticoid imbalance hypothesis has been paid more attention [7]. Glucocorticoid combined with CORT receptors (GRs) in hippocampus, prefrontal cortex and other brain regions to play roles in adjusting individual to cope with stress and form a negative feedback mechanism [2]. Cortisol concentration in the serum or saliva is increased in depressive patients [[8], [9], [10]]. Postmortem analyses of depressed suicide patients have revealed that GR mRNA level is decreased in the hippocampus and the cortex [11]. Rodent experiments have revealed that GR deficits in the prefrontal cortex of mice lead to depressive-like behaviors [12]. GR antagonist enhanced the antidepressant effect of fluoxetine [13], and the GR antagonist RU-43044 alone can also improve depressive-like behaviors in mice [14]. The antidepressant sertraline increases hippocampal neurotransmission via a GR-dependent pathway [15]. Patients with excessive glucocorticoid are more likely to experience depression recurrence. These findings suggest that CORT and their receptors are involved in the pathological process and treatment of depression [16]. But it’s still unknown whether the CORT and GRs are relevant to susceptibility or resilience. The traditional antidepressant agents such as tricyclic antidepressants, serotonin reuptake inhibitors and norepinephrine reuptake inhibitors, are aimed at inhibiting reuptake of neurotransmitter and increasing the concentration of synaptic monoamine neurotransmitters to produce antidepressant effects. These antidepressant drugs work slowly and usually it takes 4–6 weeks to achieve the effect. Furthermore, they are ineffective in about one-third of patients. Patients are still characterized by a high risk of suicide at the beginning of the treatment period [17]. The mechanism by which patients have low response to antidepressant remains unclear. Some studies suggest that hyperactivity of the HPA-axis can predict worse treatment outcome [18]. High HPA-axis activity is related with risk of relapse of depression [19]. These evidences suggest that the stress system plays an important role in the development of depression.