Imbalance in the ratio between mineralocorticoid and glucocorticoid receptors and neurodegeneration in the dentate gyrus of aged dogs

Abstract

Background and Aim: Cortisol binds to mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) found in the hippocampus. The balanced expression of these receptors is essential to neuronal survival as MR and GR activations have antiapoptotic and proapoptotic effects, respectively. Given the aging changes in dogs' dentate gyrus (DG) and the possible involvement of cortisol receptors in this process, this study aimed to evaluate the expression of MR and GR and neuronal degeneration in this hippocampal region of aged dogs. Materials and Methods: This study included cadaveric histologic hippocampus sections from six dogs aged 10 years and older (AG group) and 12 young/adult dogs aged up to 8 years (YAd group). Nissl staining and immunohistochemistry were performed to identify cells and investigate MR and GR expression, respectively. Furthermore, fluorescent labeling (fluoro- Jade B) was used to detect degenerating neurons. Results: The AG group's polymorphic layer of the DG had a lower cell count (16%) and more degenerating neurons than the YAd group. In addition to these cellular changes, the AG group had lower MR immunoreactivity and MR-to-GR ratio. Furthermore, the lowest MR expression was associated with neuronal degeneration in the polymorphic layer of the DG of dogs. Conclusion: An imbalance in the MR-to-GR ratio was observed in the polymorphic layer of the DG of aged dogs, along with lower MR expression and a greater number of degenerating neurons. These findings have clinical implications for understanding the decline in hippocampal memory formation associated with cognitive changes in aged dogs.

The relationship between worker-occupation fit and cortisol concentration of hair and plasma among medical workers

“…This hormone, in turn, activates the adrenal cortex to release cortisol the hypothalamus releases corticotropin-releasing hormone, stimulates the pituitary to distribute corticotropin-releasing hormone to the systemic circulation, and then triggers the adrenal cortex to release cortisol [22,23]. While cortisol release is bene cial in helping individuals cope with stress, excessive and prolonged exposure to cortisol can lead to hippocampal dysfunction and neuronal loss, disrupting the negative feedback regulation of the HPA axis [24,25]. This damage to hippocampal neurons weakens the inhibition of the HPA axis, causing cortisol secretion to continue increasing, thus creating a vicious circle [26].…”