The regulatory role of Gnao1 protein in diabetic encephalopathy in KK-Ay mice and streptozotocin-induced diabetic rats.

To investigate the regulation and functional role of Gnao1 in the brain of diabetic encephalopathy (DE) in various animal models. Data from the biochemical and behavioral studies showed that DE models were successful induced in streptozotocin treatment animals and KK-Ay mice. Gnao1 was down regulated in the brain tissues of these two diabetes animal models with significant cognition deficiency. It suggested that the changes in DE are also related to dementia such as Alzheimer's disease (AD). Our study also showed that the expression of adrenergic α2 receptor (Adr-α2R), the upstream protein of Gnao1, was decreased in DE animal models. Furthermore, many downstream proteins of Gnao1 also altered, among which cAMP and PKA proteins were increased, CREB and BDNF proteins were decreased both in animal models and in the cell levels. In addition, Gnao1 silencing leads to the increase of reactive oxygen species (ROS) and the decreased proliferation in cultured primary astrocytes, which means that the deficiency of Gnao1 might not be benefit for DE. Our findings demonstrated the importance of Gnao1 in DE and suggested Gnao1 as a novel marker and a promising therapeutic target for DE and dementia in animal models. Copyright © 2022 Elsevier B.V. All rights reserved.

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Shuhong Xu, Wenwen Yu, Xiang Zhang, Weiping Wang, Xiaoliang Wang. The regulatory role of Gnao1 protein in diabetic encephalopathy in KK-Ay mice and streptozotocin-induced diabetic rats. Brain research. 2022 Oct 01;1792:148012

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PMID: 35839930

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