Age-Associated Dopaminergic Neuron Loss and Midbrain Glia Cell Phenotypic Polarization. (1st September 2019) - Wang, GuoQing
Abstract: In response to changes in brain micro-environment caused by aging, microglia could polarize into proinflammatory M1 phenotype and anti-inflammatory M2 phenotype. Besides, astroglia could polarize into A1 phenotype, exhibiting neurotoxicity, or A2 phenotype, showing neuroprotection. This study aimed to investigate the change of glial cells and dopaminergic (DA) neuron in midbrain with age. Two-, 6-, 18- and 28- months old rat brains were collected. The DA neurons were detected using anti-TH and anti-DAT antibodies. The expressions of astroglia markers (glial fibrillary acidic protein, GFAP), microglia markers (ionized calcium binding adaptor molecule 1, Iba-1), M1 markers (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), M2 markers (arginase 1 (Arg1) and IL-10), A1 markers (lipocalin-2 (Lcn2) and complement C3 (C3), A2 markers (brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were examined by real time RT-PCR and Western Blotting. DA neuron expressions decreased in 18-, 28- months old rat brains. In addition, microglia and astroglia have different degrees of activation with age. Besides, M1 markers (TNF-α and IL-1β) increased and M2 markers (Arg1 and IL-10) decreased in aged rats. Furthermore, A2 markers (BDNF and GDNF) decreased and A1 markers (Lcn2 and C3) increased in aged rats. Age induced DA neuron loss and influenced midbrain glial cells phenotypic polarization, which might account for the occurrence and pathogenesis of Parkinson's diseases. Graphical abstract: Age-associated dopaminergic neuron loss and midbrain glia cell phenotypic polarization.Unlabelled Image Highlights: Age induced dopaminergic neuron loss. Age affected midbrain microglia M1/M2 phenotypic polarization. Age affected midbrain astroglia A1/A2 phenotypic polarization.