Evaluation of Behavior, Learning, Memory Along with Apoptosis, Neuronal Damage, and GABA-A Alpha-1 Receptor Level After Status Epilepticus in Immature and Mature Rats

Abstract

Objective: In this study, we aimed to evaluate age-dependent cognitive and behavioral changes, neuronal damage, and the amount of gamma-aminobutyric acid-A (GABA-A) alpha 1 in immature, mature, and adolescant rats after status epilepticus (SE). Materials and Methods: SE was induced in immature (17 days), adolescant (45 days), and mature (150 days) rats using pentylenetetrazole (PTZ). After SE, adolescant and mature rats underwent open field test and Morris water maze test. After behavioral tests, the animals were sacrificed and we performed histologic investigations on the immature, adolescant, and mature rats to assess neuronal cell damage (caspase and calpain activity) and amount of GABA-A alpha 1 receptor and compared them with a control group. Results: There were no statistically significant differences between the control and experimental groups in behavioral tests in the early stage after SE. Calpain-mediated neuronal damage was observed in mature rats with necrotic morphology after SE, but this was not observed in adolescant and immature rats. Caspase-mediated neuronal damage was observed in immature rats with apoptotic morphology after SE. The amount of GABA-A alpha 1 receptor was decreased in the three experimental groups compared with the control groups. The decrease in GABA-A alpha 1 receptor amount was highest in the mature experimental group.The amount of GABA-A alpha 1 receptor in the hippocampus decreased to level higher than in the cortex. Conclusion: This study show that there is no negative impact on learning and behavioral functions in the early stage after PTZ-induced SE, but histologically led to necrosis dominant calpain and caspase-mediated neuronal damage, calpain-mediated cell necrosis is seen particularly in the mature group and caspase-dependent apoptotic morphology observed in immature rats.The decreased of GABA-A alpha 1 receptor is highest in the adults. Our study supports that SE-induced cell damage is more pronounced with increased age, and calpain-mediated cell damage that can clearly be observed in the mature group. Long-term follow-up studies are needed to understand the long-term effect of SE-dependent neuronal damage on cognition and behavior.

Keywords

• Memory
• calpain
• caspase
• GABA receptor
• status epilepticus
• mature and immature rat