Long Noncoding RNA EBF3-AS Promotes Neuron Apoptosis in Alzheimer's Disease

AbstractPostmortem and neuroimaging studies show low levels of cortical muscarinic M1 receptors (CHRM1) in patients with schizophrenia which is significant because CHRM signalling has been shown to change levels of gene expression and cortical gene expression is altered in schizophrenia. We decided to identify CHRM1-mediated changes in cortical gene expression by measuring levels of RNA in the cortex of the Chrm1−/− mouse (n = 10), where there would be no signalling by that receptor, and in wild type mouse (n = 10) using the Affymetrix Mouse Exon 1.0 ST Array. We detected RNA for 15,501 annotated genes and noncoding RNA of which 1,467 RNAs were higher and 229 RNAs lower in the cortex of the Chrm1−/− mouse. Pathways and proteins affected by the changes in cortical gene expression in the Chrm1−/− are linked to the molecular pathology of schizophrenia. Our human cortical gene expression data showed 47 genes had altered expression in Chrm1−/− mouse and the frontal pole from patients with schizophrenia with the change in expression of 44 genes being in opposite directions. In addition, genes with altered levels of expression in the Chrm1−/− mouse have been shown to affect amyloid precursor protein processing which is associated with the pathophysiology of Alzheimer’s disease, and 69 genes with altered expression in the Chrm1−/− mouse are risk genes associated with human cognitive ability. Our findings argue CHRM1-mediated changes in gene expression are relevant to the pathophysiologies of schizophrenia and Alzheimer’s disease and the maintenance of cognitive ability in humans.

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Administration of Repetitive Transcranial Magnetic Stimulation Attenuates Aβ1-42-Induced Alzheimer’s Disease in Mice by Activating β-Catenin Signaling

BioMed Research International ◽

10.1155/2019/1431760 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Xueyun Chen ◽

Shu Chen ◽

Weidi Liang ◽

Fang Ba

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transcranial Magnetic Stimulation ◽

Neurodegenerative Disorders ◽

Water Maze ◽

Magnetic Stimulation ◽

Repetitive Transcranial Magnetic Stimulation ◽

The Brain ◽

Histological Staining ◽

Neuron Apoptosis

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive and painless technique that has been applied for the treatments of diverse neurodegenerative disorders. In the current study, its anti-Alzheimer’s disease (AD) effect was assessed and the mechanism driving the effect was explored. The AD symptoms were induced via the intracranial injection of Aβ1-42 in mice and then treated with rTMS of 1 Hz or 10 Hz. The anti-AD effect of rTMS was assessed by Morris water maze (MWM), histological staining and western blotting. The results showed that rTMS administrations of both frequencies improved the cognitive function and suppressed neuron apoptosis in AD mice. Moreover, the treatment also increased the brain BDNF, NGF, and doublecortin levels, which represented the increased viability of neurons by rTMS. The injection of Aβ1-42 also increased the expressions of p-GSK-3β, p-Tau, and p-β-catenin and suppressed the level of total β-catenin. After the treatments of rTMS, the level of β-catenin was restored, indicating the activation of β-catenin signaling. In conclusion, the findings outlined in the current study demonstrated that the anti-AD effect of rTMS was associated with the activation of β-catenin, which would promote the survival of neurons.

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