On the Developmental Timing of Stress: Delineating Sex-Specific Effects of Stress across Development on Adult Behavior

Abstract

Stress, and the chronic overactivation of major stress hormones, is associated with several neuropsychiatric disorders. However, clinical literature on the exact role of stress either as a causative, triggering, or modulatory factor to mental illness remains unclear. We suggest that the impact of stress on the brain and behavior is heavily dependent on the developmental timing at which the stress has occurred, and as such, this may contribute to the overall variability reported on the association of stress and mental illness. Here, animal models provide a way to comprehensively assess the temporal impact of stress on behavior in a controlled manner. This review particularly focuses on the long-term impact of stress on behavior in various rodent stress models at three major developmental time points: early life, adolescence, and adulthood. We characterize the various stressor paradigms into physical, social, and pharmacological, and discuss commonalities and differences observed across these various stress-inducing methods. In addition, we discuss here how sex can influence the impact of stress at various developmental time points. We conclude here that early postnatal life and adolescence represent particular periods of vulnerability, but that stress exposure during early life can sometimes lead to resilience, particularly to fear-potentiated memories. In the adult brain, while shorter periods of stress tended to enhance spatial memory, longer periods caused impairments. Overall, males tended to be more vulnerable to the long-term effects of early life and adolescent stress, albeit very few studies incorporate both sexes, and further well-powered sex comparisons are needed.

Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Ameliorated Unpredictable Chronic Mild Stress-Induced Cognitive Impairment in ICR Mice

“…Coadministration of quercetin (4) and piperine (1) attenuated UCMS-induced increased levels of TNF-α in mice brain [46]. Kaempferol (5) and rutin (7) decreased the release of pro-inflammatory cytokines by inhibiting AKT phosphorylation and NFκB activation [47]. Taken together, the present findings suggested that the memory-enhancing effects of KBD could be due to the improvement of antioxidant capacity of the flavonoid, phenolic acid, and triterpene glycosides, which are constituents of the plant ingredients, as well as the suppression of the HPA axis hyperactivation from the chronic stress exposure.…”

“…The amounts of madecassoside (2) and asiaticoside (3) found in the KBD extract were 179.35 ± 4.578 and 57.76 ± 3.003 mg/g extract, respectively. The HPLC chromatograms of ferulic acid (9), luteolin-7-O-glucoside (8), rutin (7), kaempferol-3-glucoside (6), quercetin (4), and kaempferol (5) in the KBD extract are shown in Figure S3A,B (Supplementary Materials), respectively. The amounts of ferulic acid (9), luteolin-7-O-glucoside (8), rutin (7), kaempferol-3-glucoside (6), quercetin (4), and kaempferol (5) in the KBD extract were 1.75 ± 0.128, 1.59 ± 0.464, 1.66 ± 0.289, 2.92 ± 0.063, 0.45 ± 0.039, and 0.89 ± 0.060 mg/g extract, respectively.…”

“…Accumulated evidences demonstrated that chronic stress negatively affects neural plasticity and neurogenesis which produce depressive symptom, impairment in memory and learning processes [1,2]. The deleterious effect of chronic stress is modulated by the stress hormone, cortisol/corticosterone (CORT), neurotrophins, and various neurotransmitters [3][4][5]. The repeated stress also induces the overproduction of free radicals and the suppression of antioxidant system, leading to the brain oxidative damage [6,7].…”

Effect of early life stress on anxiety and depressive behaviors in adolescent mice

“…MS has been reported to increase anxiety and depressive behaviors and cause cognitive disorder in adulthood, which was accomplished by alterations in HPA axis, decreased BDNF expression and altered structural and functional plasticity in the medial prefrontal cortex and hippocampus in rats and mice (Hennessy, Schreibeis, Schiml, & Deak, ; Musazzi et al, ; Seo et al, ; Tractenberg et al, ; Vetulani, ; van Zyl, Dimatelis, & Russell, ). Though most mental disorders in humans often begin to onset during adolescence (Kessler et al, ), previous studies in rodent models, however, mostly focused on the adult outcomes of early life stress (Schroeder, Notaras, Du, & Hill, ). Only a few numbers of studies have directly examined the effect on adolescents, and the findings were varied and inconsistent.…”

“…It was reported that adolescent female rats, not males that were exposed to social instability stress, displayed a transient increase in immobility in the forced swimming test during adolescence that diminished in adulthood (McCormick, Smith, & Mathews, 2008). The nature and severity of adverse stress, genders, and the strain of rodents are all critical elements that determine the outcomes of the effects of early life stress during adolescence (Freund, Thompson, DeNormandie, Vaccarro, & Andersen, 2013;Schroeder et al, 2018;Vetulani, 2013), and these factors may contribute to the variability of the previous results. Further studies need to clarify the roles of these factors in regulating the effect of early life stress in both adolescence and adulthood.…”