Autophagy Monitoring in Cerebral Pericytes from Alzheimer’s disease Mouse Model in an Inflammatory Environment

Abstract

Background: The blood-brain barrier (BBB) is a complex neurovascular unit involving pericytes as multi-functional cells that play a crucial role in maintaining homeostasis. In Alzheimer’s disease (AD), platelet-derived growth factor receptor-β (PDGFR β ) immunostaining revealed significantly reduced pericyte coverage of brain capillaries as well as reduced pericyte numbers in AD cortex and hippocampus compared with control brains. However, the mechanisms of pericyte loss have yet to be completely defined. Moreover, we have previously shown that, in microglia, interleukin-1 β (IL-1 β )-induced inflammation blocks autophagic flow, a physiological process involved in the degradation of proteins including the β -amyloid peptide. Thus, we evaluated whether the inflammatory response in AD impaired autophagy in pericytes. Methods: A longitudinal autophagic status monitoring was performed in pericytes purified from brains of AD and wild type (WT) mice at 3, 6 and 12 months. Furthermore, the impact of an inflammatory environment was studied not only in these primary pericytes but also in a pericyte cell line developed in the laboratory. Results: Primary pericytes from AD mice displayed a significant increase of autophagic markers at 3 months whereas in later stages their expressions were like those of WT mice. In addition, IL-1 β -induced inflammation did not modify the expression of autophagic markers and not those of mTOR signaling pathway in both primary and immortalized mouse pericytes. Conclusions: For the first time, these data highlighted that autophagy is activated in primary pericytes from AD transgenic mice at 3 months. In addition, inflammation has no impact on autophagic flow under our experimental conditions.