| First Author | Wu Q | Year | 2021 |
| Journal | Neurobiol Dis | Volume | 147 |
| Pages | 105165 | PubMed ID | 33166699 |
| Mgi Jnum | J:305153 | Mgi Id | MGI:6503647 |
| Doi | 10.1016/j.nbd.2020.105165 | Citation | Wu Q, et al. (2021) Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice. Neurobiol Dis 147:105165 |
| abstractText | Perturbed neuronal Ca(2+) homeostasis is implicated in Alzheimer's disease, which has primarily been demonstrated in mice with amyloid-beta deposits but to a lesser and more variable extent in tauopathy models. In this study, we injected AAV to express Ca(2+) indicator in layer II/III motor cortex neurons and measured neuronal Ca(2+) 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 Ca(2+) dyshomeostasis was related to pathological tau protein. Under running conditions, we found abnormal neuronal Ca(2+) activity in tauopathy mice compared to age-matched wild-type mice with higher frequency of Ca(2+) transients, lower amplitude of peak Ca(2+) transients and lower total Ca(2+) activity in layer II/III motor cortex neurons. While at resting conditions, only Ca(2+) frequency was increased. Brain levels of soluble pathological tau correlated better than insoluble tau levels with the degree of Ca(2+) dysfunction in tauopathy mice. Furthermore, tau monoclonal antibody 4E6 partially rescued Ca(2+) 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 Ca(2+) dyshomeostasis is causally linked to pathological tau protein. These findings also reveal more pronounced neuronal Ca(2+) dysregulation in tauopathy mice than previously reported by two-photon imaging that can be partially corrected with an acute tau antibody treatment. |
