Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care

Abstract

Exposures to various types of early life stress can be robust predictors of the development of psychiatric disorders, including depression and anxiety. The objective of the current study was to investigate the roles of the translationally relevant targets of central vasopressin, oxytocin, ghrelin, orexin, glucocorticoid, and the brain-derived neurotrophic factor (BDNF) pathway in an early chronic social stress (ECSS )based rodent model of postpartum depression and anxiety. The present study reports novel changes in gene expression and extracellular signal related kinase (ERK) protein levels in the brains of ECSS exposed rat dams that display previously reported depressed maternal care and increased maternal anxiety. Decreases in oxytocin, orexin, and ERK proteins, increases in ghrelin receptor, glucocorticoid and mineralocorticoid receptor mRNA levels, and bidirectional changes in vasopressin underscore related work on the adverse long-term effects of early life stress on neural activity and plasticity, maternal behavior, responses to stress, and depression and anxiety-related behavior. The differences in gene and protein expression and robust correlations between expression and maternal care and anxiety support increased focus on these targets in animal and clinical studies of the adverse effects of early life stress, especially those focusing on depression and anxiety in mothers and the transgenerational effects of these disorders on offspring.

Preadolescent Adversity Programs a Disrupted Maternal Stress Reactivity in Humans and Mice

“…This may lead to vulnerability of chronic or severe stressors experienced during pregnancy or postpartum to induce affective dysfunction. Similar to behaviors during pregnancy, PAS did not alter any behavioral measures postpartum, indicated by normal maternal care during a pup retrieval task (48). This suggests potential reprogramming of the HPA axis that lasts into the postpartum window but may be stimulus-specific, and is consistent with work showing that pup separation can alter anxiety-like behavior in postpartum females (49).…”

Effects of Chronic Social Stress and Maternal Intranasal Oxytocin and Vasopressin on Offspring Interferon-γ and Behavior

“…The CSS model of postpartum depression and anxiety (see Figure 1) depresses maternal care, impairs lactation, and increases maternal anxiety in F0 rat dams exposed to chronic male intruder stress during days 2–16 of lactation (14–16) and has similar effects in F1 and F2 dams (4, 17, 18). Juvenile and adult F2 offspring of F0 CSS dams exhibit deficits in social behavior (5).…”

“…For the F1 and F2 offspring of stressed dams, the effects of CSS on social behavior may be mediated by early-life exposure to depressed F0 maternal care and/or the male intruder stressor (F1 offspring) or depressed F1 maternal care only (F2 offspring). At the neuroendocrine level, CSS F0 dams have decreased OXT gene expression in the MeA, and CSS F1 dams also have lower MeA OXT, lower AVP in the MeA and PVN, and higher OXTR gene expression in CeA (18). CSS F2 juvenile females have higher basal serum OXT levels (5) though basal OXT levels in the CSS F1 dams do not differ (4), suggesting the transgenerational accumulation of the effects of social stress.…”

Do estresse precoce à depressão: avaliação da atividade do eixo Hipotálamo-Pituitária-Adrenal (HPA) e da função cognitiva

“…Hipotálamo-Pituitária-Adrenal (HPA) induzidas por estresse no início da vida aumentariam a vulnerabilidade para depressão na vida adulta (Juruena, Baes, Menezes, & Guilherme, 2015;Murgatroyd, Peña, Podda, Nestler, & Nephew, 2015). A análise da associação entre o estresse precoce e a depressão sugere que fatores intrínsecos aos indivíduos como sexo e predisposição genética interagem entre si modelando um fenótipo do Sistema Nervoso Central (SNC) expresso em alterações nos circuitos entre as regiões corticolímbicas e o tronco encefálico.…”

“…Os correlatos neuroanatômicos dos déficits neuropsicológicos observados em decorrência do estresse precoce se assemelham ao conjunto de estruturas e conexões afetadas pela depressão (Murgatroyd et al, 2015). Conforme tem sido bem documentado na literatura, as áreas envolvidas na patofisiologia da depressão incluem regiões do córtex pré-frontal, córtex cingulado, hipocampo, estriado, amígdala e tálamo (Nestler et al 2002;Mayberg, 1997).…”