Stress Response and Perinatal Reprogramming: Unraveling (Mal)adaptive Strategies

Abstract

Environmental stressors induce coping strategies in the majority of individuals. The stress response, involving the activation of the hypothalamic-pituitary-adrenocortical axis and the consequent release of corticosteroid hormones, is indeed aimed at promoting metabolic, functional, and behavioral adaptations. However, behavioral stress is also associated with fast and long-lasting neurochemical, structural, and behavioral changes, leading to long-term remodeling of glutamate transmission, and increased susceptibility to neuropsychiatric disorders. Of note, early-life events, both in utero and during the early postnatal life, trigger reprogramming of the stress response, which is often associated with loss of stress resilience and ensuing neurobehavioral (mal)adaptations. Indeed, adverse experiences in early life are known to induce long-term stress-related neuropsychiatric disorders in vulnerable individuals. Here, we discuss recent findings about stress remodeling of excitatory neurotransmission and brain morphology in animal models of behavioral stress. These changes are likely driven by epigenetic factors that lie at the core of the stress-response reprogramming in individuals with a history of perinatal stress. We propose that reprogramming mechanisms may underlie the reorganization of excitatory neurotransmission in the short- and long-term response to stressful stimuli.

Relaxin’ the brain: a case for targeting the nucleus incertus network and relaxin‐3/RXFP3 system in neuropsychiatric disorders

“…In humans, dysregulation of adaptive mechanisms with inappropriate and/or exaggerated responses to psychological stressors manifests as a disorder in itself and/or as a cluster of symptoms co‐morbid with other psychiatric conditions such as anxiety and depression (American Psychiatric Association, ; Gold, ). Preclinical studies that have successfully modelled mechanisms, such as plasticity and cognitive dysfunction related to stress, have furthered our understanding of the neurobiology of stress and related disorders and provided screening methods to identify new candidate drugs for treating these disorders (Kormos and Gaszner, ; Bock et al, ; Chattarji et al, ; Constantinof et al, ; Musazzi and Marrocco, ). Among the multitude of neuropeptides implicated in stress responses, the role of corticotropin‐releasing factor (CRF) is central (Aubry, ; Kormos and Gaszner, ).…”

Sex differences in ultrasonic vocalization and hormonal stress response of an anxious mice strain during the early postnatal period

“…The higher resting stress hormone levels in AX mice pups may also result in negative consequences later (Musazzi, Marrocco 2016). Moreover, the reduced stress reactivity to an immune challenge in AX mice pups is also a reflection of a disrupted coping style.…”

Examining the influence of perceived stress on developmental change in memory and perceptual speed for adopted and nonadopted individuals.

“…Moreover, periods of early-life separations predict poorer cognitive performance in humans as well, and to a lessor extent cognitive change between early and late adulthood (Pesonen et al, 2013). However, age at separation or adoption may be a moderator, such that very early adoption may mitigate or lessen risk of altered stress and cognitive functioning (e.g., Barbazanges et al, 1996; Koehl et al, 2001; van IJzendoorn, Juffer, & Klein Poelhuis, 2005), wherein HPA alterations returns to normative functioning with very early adoption and positive maternal behaviors are increased above what would be expected (Barbazanges et al, 1996; Koehl et al, 2001; Musazzi & Marrocco, 2016). HPA functioning in international adoptees who were adopted earlier (prior to 8 months) versus later (more than 1 year) were compared to non-adopted US children (Gunnar et al, 2009).…”