2025
Nateghi, Sepide; Rezayof, Ameneh; Kouhkan, Fatemeh; Delphi, Ladan; Davisaraei, Yavar Bagheri; Rostami, Fatemeh; Tirgar, Fatemeh; Sepehri, Houri
In: Brain Research Bulletin, vol. 221, pp. 111227, 2025, ISSN: 1873-2747.
Abstract | Links | BibTeX | Tags: Animal, Animals, Anxiety, Behavior, Brain Neoplasms, Cell Line, Cognition, Emotions, GABA-A, GABA-A Receptor Agonists, GABAergic signaling, GBM animal model, Glioblastoma, Male, MicroRNAs, Muscimol, Non-coding RNAs, Prefrontal Cortex, Rat(s), Rats, Receptors, Signal Transduction, Tumor, Wistar
@article{nateghi_growth_2025,
title = {Growth of the prefrontal cortical glioblastoma altered cognitive and emotional behaviors via mediating miRNAs and GABA-a receptor signaling pathways in rats},
author = {Sepide Nateghi and Ameneh Rezayof and Fatemeh Kouhkan and Ladan Delphi and Yavar Bagheri Davisaraei and Fatemeh Rostami and Fatemeh Tirgar and Houri Sepehri},
doi = {10.1016/j.brainresbull.2025.111227},
issn = {1873-2747},
year = {2025},
date = {2025-02-01},
journal = {Brain Research Bulletin},
volume = {221},
pages = {111227},
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.},
keywords = {Animal, Animals, Anxiety, Behavior, Brain Neoplasms, Cell Line, Cognition, Emotions, GABA-A, GABA-A Receptor Agonists, GABAergic signaling, GBM animal model, Glioblastoma, Male, MicroRNAs, Muscimol, Non-coding RNAs, Prefrontal Cortex, Rat(s), Rats, Receptors, Signal Transduction, Tumor, Wistar},
pubstate = {published},
tppubtype = {article}
}
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.
2022
Khodamoradi, Mehdi; Tirgar, Fatemeh; Ghazvini, Hamed; Rafaiee, Raheleh; Tamijani, Seyedeh Masoumeh Seyedhosseini; Karimi, Narges; Yadegari, Ali; Khachaki, Ali Siahposht; Akhtari, Javad
Role of the cannabinoid CB1 receptor in methamphetamine-induced social and recognition memory impairment Journal Article
In: Neuroscience Letters, vol. 779, pp. 136634, 2022, ISSN: 1872-7972.
Abstract | Links | BibTeX | Tags: 212–2, Animals, Cannabinoid, Cannabinoid CB1 receptor, Cannabinoid Receptor Antagonists, Cannabinoids, CB1, Male, Memory Disorders, Methamphetamine, Neurotoxicity Syndromes, Novel object recognition memory, Rats, Receptor, Rimonabant, Social interaction, WIN 55
@article{khodamoradi_role_2022,
title = {Role of the cannabinoid CB1 receptor in methamphetamine-induced social and recognition memory impairment},
author = {Mehdi Khodamoradi and Fatemeh Tirgar and Hamed Ghazvini and Raheleh Rafaiee and Seyedeh Masoumeh Seyedhosseini Tamijani and Narges Karimi and Ali Yadegari and Ali Siahposht Khachaki and Javad Akhtari},
doi = {10.1016/j.neulet.2022.136634},
issn = {1872-7972},
year = {2022},
date = {2022-05-01},
journal = {Neuroscience Letters},
volume = {779},
pages = {136634},
abstract = {Methamphetamine (METH) has been reported to induce social and recognition memory impairment. Evidence suggests that the cannabinoid system has an important modulatory role in cognitive processing and social interaction. Nonetheless, no previous study has investigated the probable role of the cannabinoids system on METH-induced deficits of novel object recognition (NOR) memory and social interaction. Adult male rats were given a neurotoxic METH regimen (four injections of 6 mg/kg, s.c, at 2 h intervals). One week later, they were examined for either NOR or social interaction in different groups. The cannabinoid type 1 receptor (CB1R) antagonist rimonabant (1 or 3 mg/kg, i.p.) improved METH-induced impairment of the acquisition, consolidation, and retrieval, but not reconsolidation, of NOR and also METH-induced impairment of social behavior. Administration of the CB1R agonist WIN 55,212-2 (WIN; 3 or 5 mg/kg, i.p.) did not affect memory deficits or social behavior impairment induced by METH. Our findings may indicate that METH neurotoxicity impairs social and recognition memory. On the other hand, the CB1R antagonist rimonabant, but not the CB1R agonist WIN, prevented these negative effects of METH neurotoxicity. Thus, it seems that the CB1R can be targeted to prevent the adverse effects of METH on cognition and social behavior, at least at experimental levels.},
keywords = {212–2, Animals, Cannabinoid, Cannabinoid CB1 receptor, Cannabinoid Receptor Antagonists, Cannabinoids, CB1, Male, Memory Disorders, Methamphetamine, Neurotoxicity Syndromes, Novel object recognition memory, Rats, Receptor, Rimonabant, Social interaction, WIN 55},
pubstate = {published},
tppubtype = {article}
}
Methamphetamine (METH) has been reported to induce social and recognition memory impairment. Evidence suggests that the cannabinoid system has an important modulatory role in cognitive processing and social interaction. Nonetheless, no previous study has investigated the probable role of the cannabinoids system on METH-induced deficits of novel object recognition (NOR) memory and social interaction. Adult male rats were given a neurotoxic METH regimen (four injections of 6 mg/kg, s.c, at 2 h intervals). One week later, they were examined for either NOR or social interaction in different groups. The cannabinoid type 1 receptor (CB1R) antagonist rimonabant (1 or 3 mg/kg, i.p.) improved METH-induced impairment of the acquisition, consolidation, and retrieval, but not reconsolidation, of NOR and also METH-induced impairment of social behavior. Administration of the CB1R agonist WIN 55,212-2 (WIN; 3 or 5 mg/kg, i.p.) did not affect memory deficits or social behavior impairment induced by METH. Our findings may indicate that METH neurotoxicity impairs social and recognition memory. On the other hand, the CB1R antagonist rimonabant, but not the CB1R agonist WIN, prevented these negative effects of METH neurotoxicity. Thus, it seems that the CB1R can be targeted to prevent the adverse effects of METH on cognition and social behavior, at least at experimental levels.