Abstract TP170: Heterochronic Parabiosis Lowers Microglia Activation And Myeloid Infiltration In Aged Parabiont

Abstract

Introduction: Of the 795,000 people who suffer strokes annually, 75% are over the age of 65. Aging is a major risk factor for stroke. The risk of stroke doubles every decade after the age of 55. Aging leads to dramatic changes in peripheral myeloid cells and increases the activation state of microglia in the brain. Although age is an important determinant of stroke susceptibility and outcome, the contribution from the aged immune system remains unclear. Hypothesis: We hypothesize that aged mice (18-22 mo) parabionts paired with a young parabiont (2-3 mo) would have less microglia activation due to exposure to systemic factors from young mice when compared to aged mice paired with aged mice (18-22 mo). Methods: Young Pep-boy mice (haplotype CD45.1) were surgically paired with aged mice (haplotype CD45.2) for two months. The brains of these mice were then subjected to flow cytometry analysis. Brain single cell suspensions were isolated and immunophenotyped with a microglia specific panel. Results: Our results show that myeloid infiltration was decreased in the aged parabiont (paired with a young mouse) compared to its naïve counterpart (n=3-6/ grp, p = 0.0036). Microglia activation was assessed utilizing a homeostatic marker, P2RY12, and a microglia specific marker, Tmem119. Interestingly, the expression of Tmem119 on CD45 int CD11b + cells was significantly increased in the aged parabionts compared to aged, naïve mice (n=3-6/ grp, p =0.0006), however, P2RY12 trended upward in the aged parabiont (n=3/6 /grp, p =0.0742). This suggests that the shared circulation created between the heterochronic pair led to a reduction in immune activation in the aged parabiont. Thus, the young parabiont allows the aged parabiont access to rejuvenating factors through the shared flow of blood which reduced neuroinflammation. Conclusion: Future studies are needed to identify the specific factors contributing to reduced microglial activation and lowered infiltration of peripheral immune cells induced by pairing with young animals. Studies examining the immune response to stroke in young and aged parabionts are needed.