Gut neurotoxin p-cresol induces differential expression of GLUN2B and GLUN2A subunits of the NMDA receptor in the hippocampus and nucleus accumbens in healthy and audiogenic seizure-prone rats

Gigi Tevzadze; Elene Zhuravliova; Tamar Barbakadze; Lali Shanshiashvili; Davit Dzneladze; Zaqaria Nanobashvili; Tamar Lordkipanidze; David Mikeladze

doi:10.3934/Neuroscience.2020003

Gut neurotoxin p-cresol induces differential expression of GLUN2B and GLUN2A subunits of the NMDA receptor in the hippocampus and nucleus accumbens in healthy and audiogenic seizure-prone rats

AIMS Neurosci. 2020 Mar 10;7(1):30-42. doi: 10.3934/Neuroscience.2020003. eCollection 2020.

Authors

Gigi Tevzadze¹, Elene Zhuravliova^{2

3}, Tamar Barbakadze^{2

3}, Lali Shanshiashvili^{2

3}, Davit Dzneladze³, Zaqaria Nanobashvili³, Tamar Lordkipanidze^{2

3}, David Mikeladze^{2

3}

Affiliations

¹ 4-D Research Institute, Ilia State University, 3/5 Cholokashvili av, Tbilisi, 0162, Georgia.
² Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili av, Tbilisi, 0162, Georgia.
³ I. Beritashvili Center of Experimental Biomedicine 14, Gotua Str., Tbilisi 0160, Georgia.

Abstract

Mislocalization and abnormal expression of N-methyl-D-aspartate glutamate receptor (NMDAR) subunits is observed in several brain disorders and pathological conditions. Recently, we have shown that intraperitoneal injection of the gut neurotoxin p-cresol induces autism-like behavior and accelerates seizure reactions in healthy and epilepsy-prone rats, respectively. In this study, we evaluated the expression of GLUN2B and GLUN2A NMDAR subunits, and assessed the activity of cAMP-response element binding protein (CREB) and Rac1 in the hippocampi and nucleus accumbens of healthy and epilepsy-prone rats following p-cresol administration. We have found that subchronic intraperitoneal injection of p-cresol induced differential expression of GLUN2B and GLUN2A between the two brain regions, and altered the GLUN2B/GLUN2A ratio, in rats in both groups. Moreover, p-cresol impaired CREB phosphorylation in both brain structures and stimulated Rac activity in the hippocampus. These data indicate that p-cresol differently modulates the expression of NMDAR subunits in the nucleus accumbens and hippocampi of healthy and epilepsy-prone rats. We propose that these differences are due to the specificity of interactions between dopaminergic and glutamatergic pathways in these structures.

Keywords: NMDA receptor; epilepsy; hippocampus; nucleus accumbens; p-cresol.