Abstract
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.
Highlights
Aging mice show reduced calreticulin expression in astrocytic endfeet
Aging astrocytic endfeet show dramatic changes in spontaneous Ca2+ activity
Ca2+ signals in aging endfeet depend exclusively on endoplasmic reticulum Ca2+
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Conflict of interest statement: Authors declare no competing financial interests.
CRediT author statement Sara M. Zarate: Methodology, Validation, Formal analysis, Investigation, Writing – Original draft, Writing – Review & Editing, Visualization; Taylor E. Huntington: Methodology, Writing – Review & Editing; Pooneh Bagher: Conceptualization, Methodology, Formal Analysis, Writing – Review & Editing; Rahul Srinivasan: Conceptualization, Methodology, Validation, Formal Analysis, Investigation, Resources, Writing – Original draft, Writing – Review & Editing, Visualization, Supervision, Project administration, Funding acquisition
Abbreviations
- BBB
- blood brain barrier
- NVU
- neurovascular unit
- BV
- blood vessel
- CALR
- calreticulin
- ER
- endoplasmic reticulum
- AAV
- adeno-associated virus
- PD
- Parkinson’s disease
- AD
- Alzheimer’s disease
- aCSF
- artificial cerebrospinal fluid
- DLS
- dorsolateral striatum
- AQP4
- aquaporin 4
