Chronic restraint stress induces hippocampal memory deficits by impairing insulin signaling

Abstract

Chronic stress is a psychologically significant factor that impairs learning and memory in the hippocampus. Insulin signaling is important for the development and cognitive function of the hippocampus. However, the relation between chronic stress and insulin signaling at the molecular level is poorly understood. Here, we show that chronic stress impairs insulin signaling in vitro and in vivo, and thereby induces deficits in hippocampal spatial working memory and neurobehavior. Corticosterone treatment of mouse hippocampal neurons in vitro caused neurotoxicity with an increase in the markers of autophagy but not apoptosis. Corticosterone treatment impaired insulin signaling from early time points. As an in vivo model of stress, mice were subjected to chronic restraint stress. The chronic restraint stress group showed downregulated insulin signaling and suffered deficits in spatial working memory and nesting behavior. Intranasal insulin delivery restored insulin signaling and rescued hippocampal deficits. Our data suggest that psychological stress impairs insulin signaling and results in hippocampal deficits, and these effects can be prevented by intranasal insulin delivery.

Melissa officinalis L. hydro‐alcoholic extract inhibits anxiety and depression through prevention of central oxidative stress and apoptosis

“…Our results showed increased levels of Bax and cleaved caspase 3 in the PFC and HIP of stressed mice, while Bcl‐2 was reduced, which suggest the activation of apoptosis pathways induced by stress. These findings were consistent with previous studies (Huang et al., 2015; Mohammadi et al., 2019; Woo, Hong, Jung, Choe, & Yu, 2018). Furthermore, MO reversed these changes, confirming that MO could protect against the restraint stress‐mediated neural apoptosis in the PFC and HIP.…”

“…Oxidative stress is one of the major factors that induce mitochondria‐mediated neuronal apoptosis (Méndez‐Armenta, Nava‐Ruíz, Juárez‐Rebollar, Rodríguez‐Martínez, & Yescas Gómez, 2014; Poh Loh et al., 2006). Besides, evidence shows that prolonged exposure to high concentrations of CORT can induce mitochondrial dysfunction and neuronal apoptosis (Gong, Zhang, Guo, & Fu, 2018; B. Liu et al., 2011; Woo et al., 2018). Additionally, the neuroprotective effect of RA, the main phytochemical content of MO, has been demonstrated in a large body of studies, and is mainly through suppression of oxidative stress and the apoptosis pathway (Cui et al., 2018; Khamse et al., 2018; H. J. Lee et al., 2008; Taram, Ignowski, Duval, & Linseman, 2018).…”

EA Ameliorated Depressive Behaviors in CUMS Rats and Was Related to Its Suppressing Autophagy in the Hippocampus

“…Exposure to various kinds of environmental stressors is a convincing cause to depression, by which a depression animal model, chronic unpredictable mild stress (CUMS) model, has been established and widely used [ 7 ]. Some recent researches showed autophagy alteration in CUMS animals with the reversal of behavioral effect [ 8 , 9 ].…”

Is There a Role of Autophagy in Depression and Antidepressant Action?

“…Chronic stress in mice, which frequently is used to model depression (27, 28), also has been reported to enhance autophagy [for recent examples, see Refs. (29, 30)]. The observation that a further increase in autophagic markers goes along with the reversal of the behavioral effects again argues in favor of autophagy being a beneficial component of the stress response in general (13, 30).…”