Aging reduces calreticulin expression and alters spontaneous calcium signals in astrocytic endfeet of the mouse dorsolateral striatum
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Aging-related impairment of the blood brain barrier (BBB) and neurovascular unit (NVU) increases risk for neurodegeneration. Among the various cells participating in BBB and NVU function, spontaneous Ca2+ signals in astrocytic endfeet are crucial for maintaining BBB and NVU integrity. To assess if aging is associated with changes in spontaneous Ca2+ signals within astrocytic endfeet of the dorsolateral striatum (DLS), we expressed a genetically encoded Ca2+ indicator, Lck-GCaMP6f in DLS astrocytes of young (3-4 month) and aging (20-24 month) mice. Compared to young mice, endfeet in the DLS of aging mice demonstrated a decrease in calreticulin (CALR) expression, and dramatic alterations in the dynamics of endfoot membrane-associated and mitochondrial Ca2+ signals. While young mice required both extracellular and endoplasmic reticulum (ER) Ca2+ sources for generating endfoot Ca2+ signals, aging mice showed exclusive dependence on ER Ca2+. These data suggest that aging is associated with significant changes in Ca2+ buffers and Ca2+ signals within astrocytic endfeet, which has important implications for understanding mechanisms involved in aging-related impairment of the BBB and NVU.HighlightsAging mice show reduced calreticulin expression in astrocytic endfeetAging astrocytic endfeet show dramatic changes in spontaneous Ca2+ activityCa2+ signals in aging endfeet depend exclusively on endoplasmic reticulum Ca2+Competing Interest StatementThe authors have declared no competing interest.BBBblood brain barrierNVUneurovascular unitBVblood vesselCALRcalreticulinERendoplasmic reticulumAAVadeno-associated virusPDParkinson’s diseaseADAlzheimer’s diseaseaCSFartificial cerebrospinal fluidDLSdorsolateral striatumAQP4aquaporin 4
author list (cited authors)
Zarate, S. M., Huntington, T. E., Bagher, P., & Srinivasan, R.
complete list of authors
Zarate, SM||Huntington, TE||Bagher, P||Srinivasan, R