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Selective magnetoelectric stimulation antagonizes GABAA receptors subunit in the left prelimbic cortex neurons to alleviate schizophrenia-like behaviors

ABSTRACT: Schizophrenia (SCZ) is a prevalent and disabling mental disorder. Clinically, its complex symptoms, including negative symptoms and cognitive impairments, can be ameliorated using electromagnetic techniques such as repetitive transcranial magnetic stimulation (rTMS). To investigate the neural mechanisms of magnetic stimulation and identify selective therapeutic targets, we employed a combined magnetic stimulation system treatment (c-MSST). Targeting the mouse left prelimbic cortex (PrL) with c-MSST reversed SCZ-like behaviors and dendritic spine density reductions induced by MK-801 injection. SCZ-like mice showed a region-specific increase in Gabre (gamma-aminobutyric acid type A receptor subunit epsilon) in the left PrL, normalized by c-MSST. Specific Gabre knockdown in the left PrL reversed SCZ-like behaviors induced by MK-801. Additionally, the transgenic mouse with Gabre knock-in specific to the PrL exhibited SCZ-like behaviors and synaptic plasticity deficits, both reversed by c-MSST. Overexpression of the p62 gene disrupted Gabarap and Gabarapl1 binding, reducing the surface expression of Gabre. Our findings suggest Gabre and related molecular circuits as promising targets for schizophrenia treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE286434 | GEO | 2025/01/17

REPOSITORIES: GEO

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Project description:N-Methyl-D-aspartate receptors (NMDAr), widely located around the central nervous system, are known to be involved in behavioral disorders. Dizocilpine (commonly referred to as MK-801) is a well known non-competitive NMDAr antagonist. We treated rats with intraperitoneal injection [0.08 (low-dose) and 0.16 (high-dose) mg/kg] of MK-801. In one experiment, 40 min after NaCl (vehicle control) and MK-801 (0.08 mg/kg) injection, electrocorticogram (ECoG) signals were analyzed. In the second experiment, 40 min post-injection, the whole brain of each animal was rapidly removed and separated into amyglada, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum) on ice, followed by analysis using a 4x44K DNA microarray chip. Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline (30-80 Hz) frequency oscillations. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose of MK-801. Under high-dose, ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. MK-801 increases the synchrony of baseline oscillations, causing very early changes in gene expressions in rat brain after acute MK-801 treatment, a first report. The overall goal of the present study was to identify gene expression patterns along rat chromosomes in different brain regions after a single injection of MK-801, which exerts a longer acute effect than ketamine on ongoing brain activities. Two approaches were taken, first electrophysiological and send molecular analysis, where the brain of MK-801-treated rats was subjected to a genome-wide transcriptome mapping analysis (~4400 genes) in the cerebral cortex, midbrain, hippocampus, ventral striatum, amygdala, and hypothalamus regions.

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Selective magnetoelectric stimulation antagonizes GABAA receptors subunit in the left prelimbic cortex neurons to alleviate schizophrenia-like behaviors

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