Abstract
-
J Neurochem. 2021 May;157(4):993-1012. doi: 10.1111/jnc.15234. Epub 2020 Nov
Role of Ten eleven translocation-2 (Tet2) in modulating neuronal morphology and cognition in a mouse model of Alzheimer’s disease.
Li L(1)(2), Miao M(1)(2), Chen J(3), Liu Z(4), Li W(4), Qiu Y(1)(2), Xu S(1)(2), Wang Q(1)(2).
Author information: (1)Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, Ningbo, Zhejiang, PR China. (2)Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang, PR China. (3)College of Eco-Environmental Engineering, Qinghai University, Xining, Qinghai, PR China. (4)Faculty of Physical Education, Ningbo University, Ningbo, Zhejiang, PR China.
Abnormal expression of Ten eleven translocation-2 (Tet2) contributes to the pathogenesis of Alzheimer’s disease (AD). However, to date, the role of Tet2 in modulating neuronal morphology upon amyloid-β (Aβ)-induced neurotoxicity has not been shown in a mouse model of AD. Here, we have developed a model of injured mouse hippocampal neurons induced by Aβ42 oligomers in vitro. We also investigated the role of Tet2 in injured neurons using recombinant plasmids-induced Tet2 inhibition or over-expression. We found that the reduced expression of Tet2 exacerbated neuronal damage, whereas the increased expression of Tet2 was sufficient to protect neurons against Aβ42 toxicity. Our results indicate that the brains of aged APPswe/PSEN1 double-transgenic (2 × Tg-AD) mice exhibit an increase in Aβ plaque accumulation and a decrease in Tet2 expression. As a result, we have also explored the underlying mechanisms of Tet2 in cognition and amyloid load in 2 × Tg-AD mice via adeno-associated virus-mediated Tet2 knockdown or over-expression. Recombinant adeno-associated virus was microinjected into bilateral dentate gyrus regions of the hippocampus of the mice. Knocking down Tet2 in young 2 × Tg-AD mice resulted in the same exten