Alterations in mRNA and Protein Expression of Glutamate Receptor Subunits Following Pentylenetetrazole-induced Acute Seizures in Young Rats

seizures can severely affect brain function and development. However, the underlying pathophysiological mechanisms are still poorly understood. Disturbances of the glutamatergic system are considered one of the critical mechanisms of neurological abnormalities. In the present study, we analyzed changes in the expression of NMDA and AMPA receptor subunits in the different brain regions (dorsal hippocampus, amygdala, and the medial prefrontal, temporal, and entorhinal cortex) using a pentylenetetrazole (PTZ) model of seizures in 3-week-old rats. A distinctive feature of this model is that the administration of PTZ causes severe acute seizures, which are not followed by the development of spontaneous recurrent seizures later on. Subunit expression was analyzed using qRT-PCR and Western blotting during the first week after seizures. The most pronounced alterations of mRNA and protein levels were observed in the dorsal hippocampus. We found decreased expression of the GluA2 mRNA 7 days after seizures (PSE7), as well as reduced GluN2a protein levels on PSE7. Significant alterations in the expression of different receptor subunits in the mRNA but not protein levels were observed in the entorhinal cortex and amygdala. In contrast, in the medial prefrontal and temporal cortex, we found almost no changes in the expression of the studied genes. The identified changes deepen our understanding of post-seizure disturbances in the developing brain and confirm that although various brain structures are involved in seizures, the hippocampus is the most vulnerable. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

Seizures can severely impact brain function and development, with disturbances of the glutamatergic system considered a critical mechanism of neurological abnormalities. Analysis of NMDA and AMPA receptor subunit expression in different brain regions using a rat model revealed notable changes in the dorsal hippocampus, deepening our understanding of post-seizure disturbances in the developing brain. The study confirms that although various brain structures are involved in seizures, the hippocampus is the most vulnerable.