Background: Ageing displays a low-grade pro-inflammatory profile in blood and brain. It has been documented proinflammatory cytokines accumulation leading to neuroinflammation during aging. Aged brains integrate pro inflammatory cytokines accumulation, active microglia and volumetric changes which correlates with defective cognitive performance and neurodegeneration.
Methods: Mice from 2-,12- and 20-months-old of age were submitted to different memory tests: Y-maze, Barnes maze, object location test and object location test. Afterwards, we performed structural MRI to evaluate macrostructural changes related to memory and learning regions. Following this, we also evaluated in peripheral blood and in brain tissue the presence of pro-inflammatory cytokines using the BioPlex platform. We also evaluated the presence of microglia and its morphology.
Results: We found a progressive memory loss in an age-dependent manner among in the 12- and 20-months-old mice when compared with the 2-month-old mice. Regarding the MRI, it demonstrated that the fornix volume increased the most and, the left medial entorhinal cortex showed the most volume loss. Microglia number was augmented in fornix and decreased in medial entorhinal cortex which correlated with volume gain or loss, respectively. Microglia morphology was dystrophic and activated in fornix and in a “surveillance” phenotype in the medial entorhinal cortex. We found these phenotypes to be correlated to those volume changes we found in fornix and left medial entorhinal cortex.
Conclusions: Here, we selectively identified an age-dependent proinflammatory profile and microglia activation favoring major volumetric brain changes in selective regions associated to cognitive decline in aged mice