ASTROCYTE AUTOPHAGY RESPONSE UPON NEURONAL CILIA LOSS IN THE AGING BRAIN

Abstract

Primary cilia are microtubule-based signaling organelles present in the plasma membrane of most cell types, including mature astrocytes and neurons. However, little is known about the role of this organelle in the mature brain. Data from our lab show that neuronal primary cilia (nPC) is required for soluble amyloid beta oligomer signaling and modulation of autophagy, and that these events are age dependent. Here, we hypothesize that astrocytes react to the loss of nPC and that aging might impact these events. For that purpose, we have characterized morphological changes in astrocytes as well as in the cilium and autophagy of these cells in brain tissue from young and old mice with impaired PC in neurons. Our results show that upon loss of PC in neurons astrocytes become reactive and reduce their lysosomal capacity, an effect that is reinforced with aging. Moreover, aging reduced the pool of ciliated astrocytes, which might impact their ability to react to extracellular events. Overall, our data suggest that the PC might act an intermediary in the communication between astrocytes and neurons. Highlights of the paperO_LIAstrocytes become reactive upon loss of primary cilia in neurons, which is reinforced during aging. C_LIO_LIAstrocytes in the old brain are less ciliated. C_LIO_LILoss of neuronal primary cilia decreases lysosomal capacity in astrocytes in age-dependent manner. C_LI