Research Article Open Access

Different Arrangement of Dopamine Receptors/NMDA Receptors Heterocomplexes in the Brain Regions of a Healthy Male, Female and Audiogenic Seizure-Prone Male Rats

Gigi Tevzadze1, Elene Zhuravliova2, Natia Okriashvili2, Nana Narmania2, Tamar Barbakadze2 and David Mikeladze3
  • 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

Differences in the composition and subcellular localization of heteroreceptors in the brain can trigger central nervous system diseases, including epilepsy and autism. Protein-protein interactions between Dopamine Receptors (DRs) and GLUN2A and GLUN2B subunits are critical mechanisms that regulate dopamine and glutamate coordinated signals. These interactions may be involved in the pathophysiological predisposition of epilepsy. We hypothesized that the specificity of dopaminergic neurotransmission in audiogenic Seizure-Prone (SP) rats could be underlined by the distribution and expression of the N-Methyl-D-Aspartate Glutamate Receptor (NMDAR) and Dopamine Receptor (NMDAR/DR) heterocomplex. We determined the oligomerization of synaptic and extra-synaptic NMDAR subunits with D1 and D2 receptors in the prefrontal cortex and Nucleus Accumbens (NAc) of healthy and epileptic males rats. Considering that the comorbidity of epilepsy and autism is more prevalent in females, we also studied the pattern of interaction. in NMDAR/DR heterocomplex formation in healthy female rats. The association of Dopamine Receptor type 1 (D1R) with the GLUN2A receptor, in the extra-synaptic fraction of epilepsy-prone rats, was lower than that in healthy female and male rats. In contrast, the interaction of D1R with the GLUN2B receptor was higher in the extra-synaptic membranes of epilepsy-prone rats than that in healthy rats. Furthermore, we found that the D2R/GLUN2B ratio was higher in the synaptic NAc fraction of SP and female rats. Therefore, we suggest that the different subunit proportions of the NMDAR/DR heterocomplex in the prefrontal cortex and NAc of male, female, and SP rats can be attributed to their cognitive or emotional flexibility.

American Journal of Biochemistry and Biotechnology
Volume 18 No. 2, 2022, 195-204

DOI: https://doi.org/10.3844/ajbbsp.2022.195.204

Submitted On: 22 December 2021 Published On: 27 April 2022

How to Cite: Tevzadze, G., Zhuravliova, E., Okriashvili, N., Narmania, N., Barbakadze, T. & Mikeladze, D. (2022). Different Arrangement of Dopamine Receptors/NMDA Receptors Heterocomplexes in the Brain Regions of a Healthy Male, Female and Audiogenic Seizure-Prone Male Rats. American Journal of Biochemistry and Biotechnology, 18(2), 195-204. https://doi.org/10.3844/ajbbsp.2022.195.204

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Keywords

  • NMDA Receptor
  • Dopamine Receptor
  • Epilepsy
  • Nucleus Accumbens
  • Heteroreceptor