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

Author(s)

Szriber, Shirley Jaqueline ; Novaes, Leonardo Santana ; Dos Santos, Nilton Barreto ; Munhoz, Carolina Demarchi ; Almeida Leite-Dellova, Deise Carla

• Document type: Journal article
• Source: VETERINARY WORLD; v. 15, n. 11, p. 8-pg., 2022-11-01.

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. (AU)

• FAPESP's process: 12/24002-0 - Effects of environmental enrichment in long-lasting anxiety symptoms triggered by acute stress: implications in the emotional memory acquisition
• Grantee: Leonardo Santana Novaes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/03572-3 - The relationship between glucocorticoid receptor activation and the neuronal hyperexcitability in the basolateral amygdala in the restraint stress-induced long-lasting anxiety and their implications in the impaired contextual fear extinction
• Grantee: Carolina Demarchi Munhoz
• Support Opportunities: Regular Research Grants