Publications

@article{davisaraei_nmda-receptor_2026,

title = {NMDA-receptor blockade changed microRNAs expression and apoptotic gene levels in dorsolateral striatal glioblastoma to reduce tumor growth and reverse behavioral impairments in rats},

author = {Yavar Bagheri Davisaraei and Sepide Nateghi and Ladan Delphi and Fatemeh Tirgar and Fatemeh Rostami and Maryam Sardari and Fatemeh Kouhkan and Ameneh Rezayof},

doi = {10.1016/j.neuroscience.2026.02.027},

issn = {1873-7544 0306-4522},

year  = {2026},

date = {2026-04-01},

journal = {Neuroscience},

volume = {599},

pages = {142–151},

address = {United States},

abstract = {The present study examined the involvement of the glutamatergic NMDA receptor (NMDAR) signaling pathway, specific microRNAs and apoptotic genes in the molecular and behavioral characteristics of glioblastoma multiforme (GBM) implanted into the dorsolateral striatum (DLS) in male Wistar rats. Following stereotaxic surgery, the C6 glioma cell line was implanted into the DLS to induce GBM (DLS-GBM), as confirmed by Magnetic Resonance Imaging (MRI) and Hematoxylin and Eosin (H&E) staining. Locomotor activity and exploratory behaviors were assessed using the Open Field test at 6 and 13 days post-induction of DLS-GBM, revealing alterations in these behaviors. Moreover, the DLS-GBM affected cognitive function, as animals underwent habituation followed by exposure to identical objects in the Novel Object Recognition test to assess memory performance. Repeated intra-DLS-GBM microinjections of the selective NMDAR antagonist D-AP5 (6 µg/rat) reduced the tumor volume and weight, increased survival rates, and improved behavioral outcomes. Additionally, the elevated levels of specific microRNAs (miRNAs) were associated with tumor progression, with D-AP5 lowering their expression compared to the untreated GBM group. Interestingly, D-AP5 treatment increased the expression of apoptotic genes, including Caspase-3 (9.2 folds), Caspase-9 (5.7 folds), Bax (3.5 folds), and Bak (2.7 folds), suggesting anti-tumoral effects of D-AP5 on glioblastoma cells. Taken together, these findings suggest that the blockade of NMDARs may offer therapeutic benefits by reducing tumor size and improving GBM-associated behavioral changes. Furthermore, the altered expression of specific miRNAs and apoptotic genes highlights their potential roles in GBM progression and regulatory pathways.},

keywords = {*Brain Neoplasms/metabolism/pathology/drug therapy, *Glioblastoma/metabolism/pathology/drug therapy, *MicroRNAs/metabolism, *Receptors, Animals, Apoptosis/drug effects/physiology, Cell Line, Corpus Striatum/drug effects/metabolism/pathology, D-AP5, Dorsal striatum, Excitatory Amino Acid Antagonists/pharmacology, Glioblastoma, Male, miRNAs, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism, Rat(s), Rats, Tumor, Wistar},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{tirgar_preclinical_2022,

title = {Preclinical gene therapy in glioblastoma multiforme: using olfactory ensheathing cells containing a suicide gene},

author = {Fatemeh Tirgar and Zahra Azizi and Saereh Hosseindoost and Mahmoudreza Hadjighassem},

doi = {10.1016/j.lfs.2022.121132},

issn = {1879-0631},

year  = {2022},

date = {2022-12-01},

journal = {Life Sciences},

volume = {311},

number = {Pt A},

pages = {121132},

abstract = {AIMS: Glioblastoma multiforme (GBM) is the most malignant type of brain tumor resistant to current treatments. Recently, suicide gene therapy with the Herpex Simplex Virus thymidine kinase (HSV-tk) gene has been developed with high therapeutic potency, even in clinical trials. The primary challenge to establishing a gene therapy strategy is how to transfer the desired gene into the tumor site. The olfactory ensheathing cells (OECs) secreting neurotropic and anti-inflammatory factors have a high migration capacity, making them applicable for gene therapy. We examined our new construct OECs containing the HSV-tk gene for their migration and tumoricidal ability in animal models of GBM. 

MAIN METHODS: Isolated OECs were transduced by the HSV-tk gene (OEC-tks). OEC-tks or PBS were injected ipsilaterally or contralaterally into the tumor-bearing rats, followed by gancyclovir (GCV) or PBS administration. At the end of the treatment, tumor size, apoptosis, and animal survival were assessed. 

KEY FINDINGS: Our findings demonstrated that tumor size was significantly decreased in OEC-tks ipsilateral and contralateral groups, followed by GCV injections. Furthermore, both groups' pro-apoptotic protein and gene expressions were up-regulated, whereas Bcl-2 protein expression was down-regulated. Besides, apoptosis in the OEC-tks ipsilateral/GCV group was higher in the intratumoral region, and this percentage was higher in the OEC-tks contralateral/GCV group in the peritumoral region. Interestingly, our new construct increased animal survival rate and reduced body weight loss. 

SIGNIFICANCE: OECs could serve as a novel carrier for gene therapy, have a high migration capability to the GBM and eventually suppress tumor progression.},

keywords = {Animals, Antiviral Agents, Cancer, Cultured, Ganciclovir, GCV: gancyclovir, Genetic Therapy, Glioblastoma, Glioblastoma multiforme, Olfactory ensheathing cells, Rats, Simplexvirus, Suicide gene therapy, Thymidine Kinase, Thymidine kinase gene, Tumor Cells},

pubstate = {published},

tppubtype = {article}

}