Altered expression of GABA-A receptor subunits in the hippocampus of PTZ-kindled rats

作者：Szyndler Janusz^*; Maciejak Piotr; Kolosowska Karolina; Chmielewska Natalia; Skorzewska Anna; Daszczuk Patrycja; Plaznik Adam

来源：Pharmacological Reports, 2018, 70(1): 14-21.

DOI：10.1016/j.pharep.2017.07.008

• Seizures
• PTZ kindling
• GABA-A receptor subunits
• Tonic inhibition
• Rats

Background: Changes in the expression of the GABA-A receptor subunits involved in phasic and tonic inhibition have been studied in a wide spectrum of animal models of epilepsy. However, there is no exhaustive data regarding the pentylenetetrazole (PTZ) kindling model of epilepsy.
Methods: The aim of our study was to analyse the hippocampal changes in the expression of GABA-A receptor subunits involved in phasic (alpha 1, gamma 2) or tonic (alpha 4 and delta) inhibition in rats subjected to the PTZ kindling using immunohistochemistry method as well as in animals subjected to a single injection of a subconvulsive (30 mg/kg) or convulsive (55 mg/kg) dose of PTZ. Moreover, the expression of GABA transporters (GAT-1 and GAT-3) was also assessed.
Results: In kindled animals, we observed an increase in the expression of alpha 1 (in CA1, DG (dentate gyrus) and CA3 regions) and gamma 2 (CA1 and CA3) subunits as well as in the expression of GAT-1 (CA1). On the other hand, the expression of the delta subunit in the DG was reduced. The single injection of PTZ at a dose of 30 mg/kg increased the expression of the alpha 4 subunit in the DG, while at a dose of 55 mg/kg, PTZ increased the expression of the alpha 1 and alpha 4 subunits in the DG and reduced expression of the gamma 2 subunit in the CA1 and CA3 regions.
Conclusions: The pattern of changes observed in our study indicates that changes in tonic inhibition are involved in abnormal neuronal activity observed in PTZ model of epilepsy.

• 出版日期2018-2