{"doi":"10.1101/2021.09.24.461710","title":"Aging reduces calreticulin expression and alters spontaneous calcium signals in astrocytic endfeet of the mouse dorsolateral striatum","abstract":"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 Ca 2+ signals in astrocytic endfeet are crucial for maintaining BBB and NVU integrity. To assess if aging is associated with changes in spontaneous Ca 2+ signals within astrocytic endfeet of the dorsolateral striatum (DLS), we expressed a genetically encoded Ca 2+ 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 Ca 2+ signals. While young mice required both extracellular and endoplasmic reticulum (ER) Ca 2+ sources for generating endfoot Ca 2+ signals, aging mice showed exclusive dependence on ER Ca 2+ . These data suggest that aging is associated with significant changes in Ca 2+ buffers and Ca 2+ signals within astrocytic endfeet, which has important implications for understanding mechanisms involved in aging-related impairment of the BBB and NVU. Graphical abstract Highlights Aging mice show reduced calreticulin expression in astrocytic endfeet Aging astrocytic endfeet show dramatic changes in spontaneous Ca 2+ activity Ca 2+ signals in aging endfeet depend exclusively on endoplasmic reticulum Ca 2+","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":219375,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9452,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":677364,"name":"Taylor E. Huntington","orcid":null,"position":1,"is_corresponding":false},{"id":817957,"name":"Pooneh Bagher","orcid":"0000-0002-9778-6200","position":2,"is_corresponding":false},{"id":437987,"name":"Rahul Srinivasan","orcid":"0000-0003-0237-6602","position":3,"is_corresponding":false},{"id":818628,"name":"Sara M. Zarate","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:53:38.409982Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}