Neuroinflammation increases in old and oldest-old rats except for dura mater meningeal tissue with significant gender differences: a translational perspective

Abstract

Neuroinflammaging is the nervous system version of inflammaging, the low-grade inflammation that develops with advanced age, aside from active disease or infection. Despite neuroinflammaging has been widely investigated, some important issues still need to be resolved such as the analysis of the extremely old subjects and the evaluation of specific brain areas. On this background, we conducted a study to analyze expression of inflammatory and anti-inflammatory genes in Wistar rats of different ages, including the oldest-old, in different brain regions. We found that pro-inflammatory mediators were generally up-regulated with age in cortex, hippocampus, and striatum, especially in the oldest-old group. Specifically, TNF-α showed an increment in expression with age in striatum, IL-1β and IFN-γ in hippocampus, and MCP-1 in cortex, hippocampus and striatum. Conversely, CX3CL1 and NOS2 showed a significant reduction of expression in the cortex of the oldest-old group. A different situation was observed in dura mater where TNF-α, IL-6, IL-1β, CX3CL1, and MCP-1 expression decreased in the older groups in comparison with the younger groups. With age the anti-inflammatory cytokines IL-4 and IL-10 were down-regulated in cortex, and TGF-β1 in dura mater, while IL-4 was up-regulated in the oldest-old group in hippocampus. Finally, we observed that female brains underwent an age-related increase of pro-inflammatory cytokines expression compared to males, except for striatum, and a general down-regulation of anti-inflammatory cytokines within each age group. Protein validation of selected factors by ELISA tests supported the observed changes. These data may represent a basis for future research about the neurobiology of aging, in particular in the neurodegenerative disorder framework.

Keywords: Aging; Brain; Chemokines; Cytokines; Oldest-old; Rats.