Upregulation of the lncRNA MEG3 improves cognitive impairment, alleviates neuronal damage, and inhibits activation of astrocytes in hippocampus tissues in Alzheimer's disease through inactivating the PI3K/Akt signaling pathway

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.

Depletion of LncRNA NEAT1 Rescues Mitochondrial Dysfunction Through NEDD4L-Dependent PINK1 Degradation in Animal Models of Alzheimer’s Disease

“…Liu et al, 2015). Recent studies have indicated that lncRNAs contribute to the development and progression of several brain disorders, including AD (Faghihi et al, 2008;Cao et al, 2019;Yi et al, 2019). Several differentially expressed lncRNAs were identified in human AD brains, including but not limited to n341006, LINC01094, AD-linc1, and NEAT1 (Magistri et al, 2015;Zhou and Xu, 2015;Cao et al, 2019;Zhou et al, 2019).…”

Long non‑coding RNA MEG3 knockdown alleviates hypoxia‑induced injury in rat cardiomyocytes via the miR‑325‑3p/TRPV4 axis

“…Accumulating evidence revealed that MEG3 is dysregulated in numerous complex diseases. For instance, a report on Alzheimer's disease demonstrated that MEG3 improved neuronal damage via the PI3K/AKT signaling pathway (19). Another study on non-alcoholic fatty liver disease reported that MEG3 was upregulated in high-content hydrogen water (HHW)-treated mice in contrast to the mice treated with deionized water, and MEG3 improved non-alcoholic fatty liver disease under HHW conditions via the miR-136/nuclear factor, erythroid 2 like 2 axis (20).…”

NLRC3 delays the progression of AD in APP/PS1 mice via inhibiting PI3K activation

“…In AD, the activation of glial cells leads to a series of adverse reactions, such as neuroinflammation, oxidative stress, etc. Many signal factors, including PI3K and AKT, play an important role in glial cell-activation and neuritis 28 . In bacterial LPS -induced neuritis, P13K-Akt can be activated by binding to its specific receptor and interact with multiple upstream molecules to regulate glial cell-induced neurodegeneration 29 .…”