Jiping Yi1, Bin Chen2, Xiaoxi Yao1, Yuanbiao Lei1, Fuyong Ou1, Fengzhen Huang1. 1. Department of Neurology, Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, P.R. China. 2. Department of Spinal Surgery, Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, P.R. China.
Abstract
OBJECTIVE: The purpose of this study was to elucidate the expression of the long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in rats with Alzheimer's disease (AD) and to explore its potential mechanisms. METHODS: An AD rat model was induced by microinjection of Aβ25-35 . On the first day after successful modeling, pcDNA3.1 plasmid and pcDNA3.1-MEG3 plasmid were continuously infused into the third ventricle through a micro-osmotic pump to interfere with the expression level of MEG3. The spatial learning ability and memory ability, the histopathological changes of hippocampus tissues, the ultrastructure of hippocampal neurons, astrocyte activation as well as the survival and apoptosis of hippocampal neurons in each group was observed. The expression of apoptosis, PI3/Akt signaling pathway-related proteins, glial fibrillary acidic protein, inflammatory factors, malondialdehyde, glutathione-peroxidase, and superoxide dismutase levels were determined. The deposition of amyloid beta (Aβ) in the hippocampus of rats by was observed by Aβ immunohistochemical staining. RESULTS: Downregulated MEG3 was detected in the tissues of AD rats. In addition, upregulation of MEG3 contributed to an improvement of spatial learning ability and memory ability, inhibited the pathological injury and its apoptosis of hippocampal neurons, decreased Aβ positive expression, inhibited oxidative stress injury and inflammatory injury as well as the activated astrocytes in AD rats via inactivation of the PI3/Akt pathway. CONCLUSION: Our study highlights that upregulation of the lncRNA MEG3 improves cognitive impairment, alleviates neuronal damage, and inhibits activation of astrocytes in hippocampus tissues in AD through inhibiting the PI3K/Akt signaling pathway.
OBJECTIVE: The purpose of this study was to elucidate the expression of the long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in rats with Alzheimer's disease (AD) and to explore its potential mechanisms. METHODS: An ADrat model was induced by microinjection of Aβ25-35 . On the first day after successful modeling, pcDNA3.1 plasmid and pcDNA3.1-MEG3 plasmid were continuously infused into the third ventricle through a micro-osmotic pump to interfere with the expression level of MEG3. The spatial learning ability and memory ability, the histopathological changes of hippocampus tissues, the ultrastructure of hippocampal neurons, astrocyte activation as well as the survival and apoptosis of hippocampal neurons in each group was observed. The expression of apoptosis, PI3/Akt signaling pathway-related proteins, glial fibrillary acidic protein, inflammatory factors, malondialdehyde, glutathione-peroxidase, and superoxide dismutase levels were determined. The deposition of amyloid beta (Aβ) in the hippocampus of rats by was observed by Aβ immunohistochemical staining. RESULTS: Downregulated MEG3 was detected in the tissues of ADrats. In addition, upregulation of MEG3 contributed to an improvement of spatial learning ability and memory ability, inhibited the pathological injury and its apoptosis of hippocampal neurons, decreased Aβ positive expression, inhibited oxidative stress injury and inflammatory injury as well as the activated astrocytes in ADrats via inactivation of the PI3/Akt pathway. CONCLUSION: Our study highlights that upregulation of the lncRNA MEG3 improves cognitive impairment, alleviates neuronal damage, and inhibits activation of astrocytes in hippocampus tissues in AD through inhibiting the PI3K/Akt signaling pathway.
Authors: Gita A Pathak; Frank R Wendt; Antonella De Lillo; Yaira Z Nunez; Aranyak Goswami; Flavio De Angelis; Maria Fuciarelli; Henry R Kranzler; Joel Gelernter; Renato Polimanti Journal: Circ Genom Precis Med Date: 2021-01-11