Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model

Abstract

Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer’s disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency.

Response of lactating dairy cows fed different supplemental zinc sources with and without evaporative cooling to intramammary lipopolysaccharide infusion: intake, milk yield and composition, and hematologic profile1

“…Compared with cooled cows, noncooled cows had lower average blood cortisol concentrations, consistent with Christison and Johnson (1972), who reported that prolonged exposure to heat stress reduces blood cortisol concentration. The level of supplemental Zn intake has been demonstrated to regulate hypothalamo-pituitary-adrenocortical activity and alters the glucocorticoid responses to stress or an adrenocorticotropic hormone challenge (Quarterman and Humphries, 1979;Takeda et al, 2016). However, as discussed by Quarterman and Humphries (1979), the hypothalamo-pituitary-adrenocortical sensitivity and related glucocorticoid responses to stress due to supplemental Zn are inconsistent across different species.…”

Inhibition of Phosphodiesterase 4 by FCPR03 Alleviates Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of p38 and JNK Signaling Pathways

“…Chronic activation of the HPA axis promotes the secretion of adrenocorticotrophic hormone from the pituitary gland, which ultimately leads to the abnormally-increased levels of glucocorticoids from the adrenal cortex [ 4 ]. Excessive glucocorticoids in the brain impairs hippocampal granule cells and increases susceptibility to various stressful situations, including depression [ 37 , 41 ]. In the present study, the endocrine changes in the HPA axis were observed following LPS administration.…”

Interaction between Zinc, GPR39, BDNF and Neuropeptides in Depression

“…Its hypersecretion is linked to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA), which is normalized following successful antidepressant treatment [ 37 ]. Hyperactivity of the HPA is observed under zinc-deficient conditions conditions that correlate with depression-like behavior [ 38 ]. In one study, young rats fed a diet low in zinc were exposed to acute stress.…”