Effects of Acute Confinement Stress-induced Hypothalamic-pituitary Adrenal Axis Activation and Concomitant Peripheral and Central Transforming Growth Factor-β1 Measures in Nonhuman Primates

Abstract

Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine with anti-inflammatory, immunosuppressive and neuroprotective properties. The hypothalamic-pituitary-adrenal (HPA) axis and immune system exert bidirectional influences on each other, via cortisol and TGF-β1, but the exact nature of the interaction is not well characterized. The current study examined the effects, in bonnet macaques (Macaca radiata), of two consecutive acute confinement stress periods in an unfamiliar room while mildly restrained, first without and then with dexamethasone pretreatment (0.01 mg/kg IM). Preceding the confinement studies, a non-stress control condition obtained contemporaneous levels of cortisol and TGF-β1 in both plasma and cerebrospinal fluid (CSF) to match the confinement stress studies. Subjects were reared under either normative or variable foraging demand (VFD) conditions. Since there were no rearing effects at baseline or for any of the conditions tested -- either for cortisol or TGF-β -- the study analyses were conducted on the combined rearing groups. The stress condition increased both plasma and CSF cortisol levels whereas dexamethasone pretreatment decreased cortisol concentrations to below baseline levels despite stress. The stress condition decreased TGF-β1 concentrations only in CSF but not in serum. Together the data suggested that stress-induced reductions of a centrally active neuroprotective cytokine occurs in the face of HPA axis activation, potentially facilitating glucocortoid-induced neurotoxicity. Stress-induced reductions of neuroprotective cytokines prompts exploration of protective measures against glucocorticoid-induced neurotoxicity.

Endocrine disruptors also function as nervous disruptors and can be renamed endocrine and nervous disruptors (ENDs)

“… Li et al [ 165 ]: provides robust ischemic neuroprotection but also exerts neurotoxicity when administered during ischemia and early reperfusion. 60 Dexamethasone Synthetic steroid Coplan et al [ 166 ]: glucocorticoid-induced neurotoxicity. Yu et al .…”

Prenatal stress induces a depressive-like phenotype in adolescent rats: The key role of TGF-β1 pathway

“…It is also possible that no correlation exists between a central deficit of TGF-β1 after PNS procedure and the reduced levels of this cytokine in the periphery. A recent study conducted in non-human primates, exposed to two consecutive acute confinement stress periods, seems to suggest this hypothesis, with the stress condition able to decrease TGF-β1 concentrations only in cerebrospinal fluid, but not in serum (Coplan et al, 2017).…”

Ancestral Food Sources Rich in Polyphenols, Their Metabolism, and the Potential Influence of Gut Microbiota in the Management of Depression and Anxiety

“…In this context, the confinement of the population caused by COVID-19 is considered a cause that has led to stress states and consequent diminishing of the neurogenesis process, especially in vulnerable subjects, as demonstrated in studies carried out on nonhuman animals. Thus, Coplan et al indicate that acute confinement of primates tends to promote states of depression and anxiety that correlate with elevated cortisol levels. Furthermore, other authors have indicated the monitoring of important biomarkers which have been used to screen drugs and bioactive compounds with antidepressant potential. − …”