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Growth of the Prefrontal Cortical Glioblastoma Altered Cognitive and Emotional Behaviors Via Mediating Mirnas and Gaba-A Receptor Signaling Pathways in Rats Publisher Pubmed



Nateghi S1 ; Rezayof A1 ; Kouhkan F2 ; Delphi L1 ; Davisaraei YB1 ; Rostami F2 ; Tirgar F3, 4 ; Sepehri H1
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Authors Affiliations
  1. 1. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
  2. 2. Stem Cell Technology Research Center (STRC), Iran University of Medical Sciences (IUMS), Tehran, Iran
  3. 3. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Iranian National Center for Addictions Studies, Tehran University of Medical Sciences, Tehran, Iran

Source: Brain Research Bulletin Published:2025


Abstract

The present study investigated the impact of GABAergic signaling and miRNA expression on glioblastoma multiforme (GBM) growth within the medial prefrontal cortex (mPFC) and its associated cognitive and emotional impairments. The implantation of C6 cells into the mPFC induced GBM in this brain region (referred to as the mPFC-GBM) in male Wistar rats via stereotaxic surgery, as confirmed by Magnetic Resonance Imaging (MRI), and Hematoxylin and Eosin (H&E) staining. Repeated microinjections of muscimol, a potent GABAA receptor agonist, directly into the mPFC-GBM (1 µg/rat/2.5 μl) following tumor induction decreased tumor volume and weight, resulting in an increased survival rate. Conversely, a higher dose of muscimol (6 µg/rat/2.5 μl) increased tumor size and reduced survival. Behavioral alterations induced by GBM, including anxiety-like responses, exploratory behaviors, locomotor activity, and memory formation, were assessed using anxiety-like behavior task, the hole-board test, and the novel object recognition test. Muscimol treatment dose-dependently affected these behaviors in the animals with the mPFC-GBM, bringing their performance with that of the sham group at the dose of 1 µg/rat/2.5 μl. Changes in specific miRNAs expressions, including miR-208, −290–295, −345, −743 and −802 were associated with the growth of the mPFC-GBM under muscimol treatment. These findings suggest that GBM growth into the mPFC profoundly impacts cognitive and emotional behaviors which can be improved by muscimol treatment. Considering that the expression levels of targeted miRNAs could be influenced by the growth of the mPFC-GBM, both with or without muscimol treatment, these non-coding RNAs might serve as potential biomarkers for GBM. © 2025 The Authors
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