Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice
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 neur...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999612030440X |
| _version_ | 1818673095920058368 |
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| author | Qian Wu Yang Bai Wei Li Erin E. Congdon Wenke Liu Yan Lin Changyi Ji Wen-Biao Gan Einar M. Sigurdsson |
| author_facet | Qian Wu Yang Bai Wei Li Erin E. Congdon Wenke Liu Yan Lin Changyi Ji Wen-Biao Gan Einar M. Sigurdsson |
| author_sort | Qian Wu |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T07:50:21Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-e5c4ccb26c1843cf9df2959327faf0202022-12-21T21:57:53ZengElsevierNeurobiology of Disease1095-953X2021-01-01147105165Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy miceQian Wu0Yang Bai1Wei Li2Erin E. Congdon3Wenke Liu4Yan Lin5Changyi Ji6Wen-Biao Gan7Einar M. Sigurdsson8New York University Grossman School of Medicine, Department of Neuroscience and Physiology, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Neuroscience Institute, Science Building, 435 East 30th Street, New York, NY 10016, United States of AmericaNew York University Grossman School of Medicine, Department of Neuroscience and Physiology, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Neuroscience Institute, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Skirball Institute, 550 First Avenue, New York, NY 10016, United States of AmericaNew York University Grossman School of Medicine, Department of Neuroscience and Physiology, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Neuroscience Institute, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Skirball Institute, 550 First Avenue, New York, NY 10016, United States of AmericaNew York University Grossman School of Medicine, Department of Neuroscience and Physiology, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Neuroscience Institute, Science Building, 435 East 30th Street, New York, NY 10016, United States of AmericaNew York University Grossman School of Medicine, Department of Psychiatry, 550 First Avenue, New York, NY 10016, United States of AmericaNew York University Grossman School of Medicine, Department of Neuroscience and Physiology, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Neuroscience Institute, Science Building, 435 East 30th Street, New York, NY 10016, United States of AmericaNew York University Grossman School of Medicine, Department of Neuroscience and Physiology, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Neuroscience Institute, Science Building, 435 East 30th Street, New York, NY 10016, United States of AmericaNew York University Grossman School of Medicine, Department of Neuroscience and Physiology, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Neuroscience Institute, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Skirball Institute, 550 First Avenue, New York, NY 10016, United States of AmericaNew York University Grossman School of Medicine, Department of Neuroscience and Physiology, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; New York University Grossman School of Medicine, Neuroscience Institute, Science Building, 435 East 30th Street, New York, NY 10016, United States of America; Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, United States of America; Corresponding author at: Department of Neuroscience and Physiology, New York University Grossman School of Medicine, Neuroscience Institute, Science Building, Room 1115, 435 E 30th Street, New York, NY 10016, United States of America.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.http://www.sciencedirect.com/science/article/pii/S096999612030440XAlzheimer's diseaseFrontotemporal dementiaTauAntibodyCa2+Two-photon imaging |
| spellingShingle | Qian Wu Yang Bai Wei Li Erin E. Congdon Wenke Liu Yan Lin Changyi Ji Wen-Biao Gan Einar M. Sigurdsson Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice Neurobiology of Disease Alzheimer's disease Frontotemporal dementia Tau Antibody Ca2+ Two-photon imaging |
| title | Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice |
| title_full | Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice |
| title_fullStr | Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice |
| title_full_unstemmed | Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice |
| title_short | Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice |
| title_sort | increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice |
| topic | Alzheimer's disease Frontotemporal dementia Tau Antibody Ca2+ Two-photon imaging |
| url | http://www.sciencedirect.com/science/article/pii/S096999612030440X |
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