{"doi":"10.1016/j.nbd.2020.105165","title":"Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice","abstract":"Perturbed neuronal Ca2+ homeostasis is implicated in Alzheimer's disease, which has primarily been demonstrated in mice with amyloid-β deposits but to a lesser and more variable extent in tauopathy models. In this study, we injected AAV to express Ca2+ indicator in layer II/III motor cortex neurons and measured neuronal Ca2+ activity by two photon imaging in awake transgenic JNPL3 tauopathy and wild-type mice. Various biochemical measurements were conducted in postmortem mouse brains for mechanistic insight and a group of animals received two intravenous injections of a tau monoclonal antibody spaced by four days to test whether the Ca2+ dyshomeostasis was related to pathological tau protein. Under running conditions, we found abnormal neuronal Ca2+ activity in tauopathy mice compared to age-matched wild-type mice with higher frequency of Ca2+ transients, lower amplitude of peak Ca2+ transients and lower total Ca2+ activity in layer II/III motor cortex neurons. While at resting conditions, only Ca2+ frequency was increased. Brain levels of soluble pathological tau correlated better than insoluble tau levels with the degree of Ca2+ dysfunction in tauopathy mice. Furthermore, tau monoclonal antibody 4E6 partially rescued Ca2+ activity abnormalities in tauopathy mice after two intravenous injections and decreased soluble pathological tau protein within the brain. This correlation and antibody effects strongly suggest that the neuronal Ca2+ dyshomeostasis is causally linked to pathological tau protein. These findings also reveal more pronounced neuronal Ca2+ dysregulation in tauopathy mice than previously reported by two-photon imaging that can be partially corrected with an acute tau antibody treatment.","journal":"Neurobiology of Disease","year":2020,"id":70710,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260401,"name":"Yang Bai","orcid":"0000-0002-6618-8929","position":1,"is_corresponding":false},{"id":374057,"name":"Wei Li","orcid":"0000-0002-9258-3500","position":2,"is_corresponding":false},{"id":367656,"name":"Erin E. Congdon","orcid":"0000-0001-8322-6176","position":3,"is_corresponding":false},{"id":374058,"name":"Wenke Liu","orcid":"0000-0002-0558-6827","position":4,"is_corresponding":false},{"id":374059,"name":"Yan Lin","orcid":"0009-0005-9357-4832","position":5,"is_corresponding":false},{"id":374060,"name":"Changyi Ji","orcid":"0000-0002-0846-7954","position":6,"is_corresponding":false},{"id":260405,"name":"Wen‐Biao Gan","orcid":"0000-0002-5620-7276","position":7,"is_corresponding":false},{"id":291810,"name":"Einar M. Sigurdsson","orcid":"0000-0003-1451-0952","position":8,"is_corresponding":false},{"id":367655,"name":"Qian Wu","orcid":"0000-0002-8912-0118","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T21:43:32.585486Z","pmid":"33166699","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":[]}