P1.36. MODULATION OF NMDA RECEPTOR SUBUNIT EXPRESSION BY (R,S)-SULFORAPHANE IN THE OLFACTORY BULBECTOMY MODEL IN MICE
Bernadetta Jakubowska1, Magdalena Sowa-Kućma2,,3, Przemysław Sołek4,,5, Patrycja Pańczyszyn-Trzewik2
1 Students Science Club "NEURON", Faculty of Medicine, Collegium Medicum, University of Rzeszów, Rzeszow, Poland
2 Department of Human Physiology, Faculty of Medicine, Collegium Medicum, University of Rzeszów, Rzeszow, Poland
3 Centre for Innovative Research in Medical and Natural Sciences, Faculty of Medicine, Collegium Medicum, University of Rzeszów, Rzeszow, Poland
4 Department of Biochemistry and Toxicology, University of Life Sciences, Lublin, Poland
5 Department of Biopharmacy, Medical University of Lublin, Lublin, Poland
INTRODUCTION: Dysregulation of glutamatergic transmission via NMDA receptors is increasingly recognized as a key contributor to the pathophysiology of depression . The olfactory bulbectomy (OB) is a well-established animal model that displays behavioral and molecular features characteristic of agitated depression. (R,S)-Sulforaphane (SFN) is a bioactive compound known for its antioxidant and neuroprotective properties, primarily through activation of Nrf2 pathway. Emerging evidence suggests its potential to modulate glutamatergic signaling and antidepressant-like activity . However, its influence on NMDA receptor subunit expression in depression remains unclear.
AIM(S): Investigation the effects of repeated SFN treatment on GluN2A and GluN2B expression in the frontal cortex (FCx) and hippocampus (Hp) in OB mice.
METHOD(S): Brain samples (FCx and Hp) were obtained from mice subjected to the OB procedure followed by 14-day treatment with (R,S)-sulforaphane (10 mg/kg i.p.; SFN10). Control (Sham) and reference drug (Amitriptyline 10 mg/kg i.p.; AMI10) groups were included in this study. Protein levels of GluN2A and GluN2B were determined by Western blot, and mRNA levels of Grin2a and Grin2b were assessed using Real-Time PCR. Statistical analysis was conducted with one-way ANOVA (GraphPad Prism v10.0).
RESULTS: OB procedure did not significantly change on GluN2A and GluN2B protein levels, both in the FCx and Hp. However, SFN10 treatment significantly decreased GluN2B protein levels in the FCx of OB mice (p<0.01), with no changes observed in the Hp. At the mRNA level, OB had no significant effect on Grin2a or Grin2b expression. Notably, both SFN10 and AMI10 (R,S) significantly reduced Grin2b mRNA levels in the FCx of OB mice (p<0.001). In contrast, only SFN10 induced a significant increase in Grin2b expression in the Hp (p<0.05). SFN 10 and AMI10 treatment did not affected Grin2a mRNA expression in either brain region.
CONCLUSIONS: These findings indicate that (R,S)-sulforaphane may in modulate NMDA receptor subunits expression in a specific brain region. Moreover, the obtained results suggest a potential molecular target involved in this regulation, specifically related to the GluN2B subunit.
FINANCIAL SUPPORT: The study was partially supported by the PRELUDIUM grant from the National Science Centre contract: UMO-2016/23/N/NZ4/01337 provided to P. Pańczyszyn-Trzewik.