Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice.
Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice.
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运动皮层中的神经元活性增加表明，扭曲小鼠的显着钙dy症。
DOI：
10.1016/j.nbd.2020.105165
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发表时间：
2021-01
影响因子：
6.1
通讯作者：
Sigurdsson EM
中科院分区：
文献类型：
--
作者：
Wu Q;Bai Y;Li W;Congdon EE;Liu W;Lin Y;Ji C;Gan WB;Sigurdsson EM
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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影响因子：
4.6
作者：
Imamura K;Sahara N;Kanaan NM;Tsukita K;Kondo T;Kutoku Y;Ohsawa Y;Sunada Y;Kawakami K;Hotta A;Yawata S;Watanabe D;Hasegawa M;Trojanowski JQ;Lee VM;Suhara T;Higuchi M;Inoue H
通讯作者：
Inoue H
影响因子：
7.8
作者：
Baglietto-Vargas D;Prieto GA;Limon A;Forner S;Rodriguez-Ortiz CJ;Ikemura K;Ager RR;Medeiros R;Trujillo-Estrada L;Martini AC;Kitazawa M;Davila JC;Cotman CW;Gutierrez A;LaFerla FM
通讯作者：
LaFerla FM
影响因子：
1.9
作者：
Kamat PK;Kalani A;Tyagi N
通讯作者：
Tyagi N
影响因子：
5.3
作者：
Castillo-Carranza, Diana L.;Sengupta, Urmi;Kayed, Rakez
通讯作者：
Kayed, Rakez
影响因子：
15.1
作者：
Lasagna-Reeves CA;Castillo-Carranza DL;Sengupta U;Clos AL;Jackson GR;Kayed R
通讯作者：
Kayed R