Dysregulated Hypothalamic–Pituitary–Adrenal Axis Function Contributes to Altered Endocrine and Neurobehavioral Responses to Acute Stress

Abstract

Organisms react to environmental challenges by activating a coordinated set of brain–body responses known as the stress response. These physiological and behavioral countermeasures are, in large part, regulated by the neuroendocrine hypothalamic–pituitary–adrenal (HPA) axis. Normal functioning of the HPA axis ensures that an organism responds appropriately to altered environmental demands, representing an essential system to promote survival. Over the past several decades, increasing evidence supports the hypothesis that disruption of the HPA axis can lead to dysregulated stress response phenotypes, exacting a physiological cost on the organism commonly referred to as allostatic load. Furthermore, it has been recognized that high allostatic load can contribute to increased vulnerability of the organism to further challenges. This observation leads to the notion that disrupted HPA function and resulting inappropriate responses to stressors may underlie many neuropsychiatric disorders, including depression and anxiety. In the present set of studies, we investigate the role of both the normally functioning and disrupted HPA axis in the endocrine, neural, and behavioral responses to acute stress. Using a model of non-invasive chronic corticosterone treatment in mice, we show that dysregulating the normal function of the HPA leads to a mismatch between the hormonal and neural response to acute stress, resulting in abnormal behavioral coping strategies. We believe this model can be leveraged to tease apart the mechanisms by which altered HPA function contributes to neurobehavioral dysregulation in response to acute stress.

Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation

“…The 2,869 downregulated genes were mainly involved in metabolic processes, development process, DNA biosynthesis adjustment process, the cardiovascular system, cell adhesion, cell migration and positioning process. It has been shown that under acute stress conditions, mesenchymal stem cells and endothelial progenitor cells mobilize and provide a significant response, while HPA axia response and its key effect hormones-glucocorticoids exert an important regulatory effect (45–47). Additionally, researchers have found that the gene expression of early BMSCs played a supporting role in nerve repair in the development of the nervous system (48), and the endogenous ligand of rat-derived BMSCs could be anti-apoptotic (49).…”

Sustained glucocorticoid exposure recruits cortico-limbic CRH signaling to modulate endocannabinoid function

“…Techniques for riboprobe synthesis are described in greater detail elsewhere (Makino et al, 1994b). A thorough description of tissue preparation and the in situ hybridization protocol can also be found elsewhere (Kinlein et al, 2015). Based on the strength of autoradiographic signal on test slides exposed to X-ray film (Kodak BioMax MR film, Sigma, St. Louis, MO, USA), hybridized slides containing the PFC were exposed to film for 2 days to optimize the detection of possible treatment differences.…”

Therapeutic implications of the choroid plexus–cerebrospinal fluid interface in neuropsychiatric disorders

“…For example, treatment with IFNa induces major depression and this effect is, amongst others, related to alterations in the HPA axis (Castanon et al, 2014). The development of PTSD is also associated with HPA dysfunction, however, it is unclear whether this concerns hypo-or hyperfunction of the HPA axis (Kinlein et al, 2015). Finally, evidence grows that an altered communication across the gut-brain axis is associated with inflammatory-driven neuropsychiatric disorders (Castanon et al, 2014;Collins et al, 2012).…”