Work

GABAA receptor-acting neurosteroids: A role in the development and regulation of the stress response

Year: 2014

Type: review

Abstract: Regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity by stress is a fundamental survival mechanism and HPA-dysfunction is implicated in psychiatric disorders. Adverse early life experiences, e.g. poor maternal care, negatively influence brain development and programs an abnormal stress response by encoding long-lasting molecular changes, which may extend to the next generation. How HPA-dysfunction leads to the development of affective disorders is complex, but may involve GABAA receptors (GABAARs), as they curtail stress-induced HPA axis activation. Of particular interest are endogenous neurosteroids that potently modulate the function of GABAARs and exhibit stress-protective properties. Importantly, neurosteroid levels rise rapidly during acute stress, are perturbed in chronic stress and are implicated in the behavioural changes associated with early-life adversity. We will appraise how GABAAR-active neurosteroids may impact on HPA axis development and the orchestration of the stress-evoked response. The significance of these actions will be discussed in the context of stress-associated mood disorders.

Source: Frontiers in Neuroendocrinology

DOI: 10.1016/j.yfrne.2014.06.001

Authors: Benjamin G. Gunn, Linda Cunningham, Scott G. Mitchell, Jerome D. Swinny, Jeremy J. Lambert, Delia Belelli

Institutions: University of Dundee, Ninewells Hospital, University of Portsmouth

Language: English

Topic: Stress Responses and Cortisol

Subfield: Behavioral Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,800