Ions phagocytosis of Syn accumulations probably isn’t a part of the protective program of microglia with lengthy telomeres. Our information linking elevated LXR/ RXR signaling and prolonged survival of SYNtg/tganimals would recommend a protective function of this signaling pathway also in our Parkinson’s disease model. In such situation wild form microglia would respond for the presence of Syn accumulating neurons with improved LXR/RXR signaling. No FGF-basic/bFGF protein Bovine matter whether this hypothesis holds correct and how enhanced LXR/RXR signaling in microglia lastly protects from Syn pathology remains to become investigated. Even though significantly remains to be learned regarding the distinctive microglia responses and their impact on Syn pathology and also the survival of animals, our data point towards an aging associated dysfunction of microglia, which negatively influence neurodegeneration. Microglia in the aged brainhave been suggested to become primed for activation, meaning that they obtain a state of exaggerated inflammatory reactivity and/or persistent neuroinflammation. As such microglia priming is deemed an important confounding issue in age-associated neurodegenerative diseases [79, 80]. On the other hand, dystrophic microglia, characterized by loss of IGSF11 Protein C-Fc structural integrity, presence of spheroid inclusions and fragmented cellular processes have already been reported in the aged human brain [81] or in rodent mouse models of accelerated aging and neurodegeneration [82, 83]. Due to the fact dystrophy in microglia is restricted to aged and neurodegenerative brain tissues, it has been proposed to become the consequence of age-associated telomere shortening and replicative senescence in microglia [36]. In contrast to primed microglia, dystrophic microglia have already been suggested to become functionally impaired. As a direct consequence the brain becomes far more vulnerable potentially major to neurodegenerative illness [84]. Whether or not telomere shortening in vivo includes a direct influence on microglia functionality is at present unclear. We previously demonstrated that telomere shortening didn’t influence basal microglia gene expression pattern or unchallenged microglia functions [73], which is in agreement together with the right here presented data. Having said that, in spite of the lack of a morphological response we here also show that microglia with brief telomeres displayed a clearly unique reaction at the mRNA level inside the presence of Syn pathology. It was surprising to find out that microglia with an indistinguishable mRNA expression pattern showed a different response towards pathology and to our information such an observation has not however been published elsewhere. The reason for this peculiar acquiring is not clear in the moment, but nonetheless clearly indicating that short telomeres influences microglia gene expression and functionality in response to brain pathology. Despite the fact that telomere shorting has been described for microglia [346] we can not exclude effects in other cells. Our information also show that the response of astrocyte is impaired in TERC-/- mice with Syn pathology. As there is little if any information about telomere shortening in astrocytes [34] it is unclear no matter whether this impaired astrocyte response to directly because of the knockout of telomerase in astrocytes. Far more probably might be that astrocytes responded differently towards the changed inflammatory reaction in TERC-/- animals. Furthermore, we’ve not too long ago shown variations in blood brain barrier (BBB) function in third generation TERC-/animals resulting in elevated infiltration in the brain in peripheral i.