Specific deletion connexin43 in astrocyte ameliorates cognitive dysfunction in APP/PS1 mice

Life Sciences
Runan RenMin Wang

Abstract

Emerging data indicate an important role for connexin43 (Cx43) in cognitive function, but there is a lack of direct evidence of the role of astroglial Cx43 in cognitive dysfunction in Alzheimer's disease (AD). Here we evaluated the expression pattern of Cx43 in AD and found progressive upregulation of the mRNA and protein levels of Cx43. Subsequently, we generated an astroglial Cx43 knockout (KO) AD mouse model by crossbreeding Gfap (glial fibrillary acidic protein)-Cx43 KO mice with APP/PS1 mice. Then we assessed the cognitive function of 12-month-old APP (amyloid precursor protein)/PS1 (presenilin 1)/Gfap-Cx43 KO mice, which demonstrated that the deletion of astroglial Cx43 significantly ameliorated cognitive dysfunction. To further investigate the underlying mechanisms, we evaluated amyloid plaque formation, astrogliosis, and synaptic function. The number and area of amyloid plaques were not altered, but GFAP expression was significantly decreased and the number of synapses was markedly upregulated. These results suggest that deletion of astroglial Cx43 in APP/PS1 mice did not affect the formation of amyloid plaques but depressed astrogliosis and upregulated synaptic function. Moreover, levels of critical modulators of astro...Continue Reading

Citations

Sep 1, 2019·Current Alzheimer Research·Laura Trujillo-EstradaFrank M LaFerla
Dec 24, 2019·Bioscience Reports·Jin-Ting HeXin Zhao
Dec 24, 2018·Acta Neuropathologica Communications·Yuji KajiwaraBin Zhang
Feb 23, 2019·Frontiers in Molecular Neuroscience·LingYan XingGang Chen
Apr 25, 2020·Physiological Reviews·Christian GiaumeLuc Leybaert
Sep 2, 2020·The Journal of Biological Chemistry·Mahua MaulikJayasri Das Sarma
Jan 6, 2021·Biomolecules·Marc MesnilDenis Sarrouilhe
Feb 4, 2021·International Journal of Molecular Sciences·Shon A KorenJose F Abisambra
Apr 4, 2021·Ageing Research Reviews·Brittani R PriceChristopher M Norris
Jun 15, 2021·Frontiers in Molecular Neuroscience·Xiaomin HuangChenju Yi

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