Neuronal and glial region dependent changes in female mice from a model of premature aging

Adult Premature Aging Mice (PAM) show premature immunosenescence, oxidative and inflammatory stress and consequently a shorter lifespan than Exceptional Non-Prematurely Aging Mice (E-NPAM) at the same age. Indeed, adult female PAM exhibit behavioral age-related declines and abnormalities in its brain neurochemistry. Nevertheless, it is not clear whether these impairments might be accompanied by previous changes related to the neuroinflammation process in their central nervous system (CNS). Therefore, the aim of the present work was to determine if adult female PAM may show brain neuroinflammation processes comparable to those observed in chronologically old female mice. Accordingly, ICR-CD1 female mice were classified in PAM, Regular Non-Prematurely Aging Mice (R-NPAM) and E-NPAM and compared to a group of chronologically old female mice (OLD) (24±1 months). Through the application of immunohistochemical techniques we evaluated changes in the expression of NeuN (a neuronal marker), Iba-1 (a microglia marker) and GFAP (an astrocyte marker) in brain areas related to the behavioral alterations previously detected in both PAM and chronologically old mice. In general, PAM showed a lower NeuN expression and a higher GFAP and Iba1 expression mainly in the Anterior Frontal Cortex and in the Medial Hippocampal Formation, when compared to E-NPAM; similar changes were observed in OLD. Other brain areas, such as the Hypothalamic Nuclei and Motor Cortex were less affected. In conclusion, adult PAM and OLD female mice share some region-dependent neuronal and glial changes that may underlie, at least in part, some of the behavioral abnormalities previously reported in these animals.