Maturational effects of single and multiple early-life seizures on AMPA receptors in prepubescent hippocampus

Abstract

The effects of single versus multiple episodes of status epilepticus on the expression of AMPA receptors during a critical growth spurt are unknown. To determine whether the pattern of hippocampal AMPA receptor subunit expression depends upon the age of the animal, timing and number of perinatal seizures, we characterized maturational changes in AMPA receptor protein levels of the hippocampus with immunohistochemistry and Western blotting in rats of juvenile ages with and without a history of neonatal seizures. Kainic acid (KA) was used to induce a single episode of status epilepticus (1 x KA) in rats on P20 or P30. Animals with a history of multiple seizures (3 x KA) were given KA on P6, P9, and then on P20 or P30. After 1 x KA, in P20 and P30 rats that are preferentially sensitive to CA1 damage, GluR1 immunoreactivity was depleted remarkably in CA1 stratum pyramidale and stratum lucidum and only morphologically healthy cells were faintly labeled. At P30, GluR2 subunit expression was nearly absent in the healthy cells and increased within the injured CA1 neuronal population. Western blot analysis confirmed that the GluR1/GluR2 ratio was decreased at P20 and further decreased at P30. A history of perinatal seizures (3 x KA) prevented the age-dependent alterations in the CA1. Except for areas of cell loss, NR1 and NR2A/B antibody labeling was relatively stable throughout the hippocampus at both ages and conditions examined. Data suggest that (i) Ca2+ permeable AMPA receptors may not be responsible for neuronal injury or irreversible cell loss and that (ii) the expression of AMPA receptors after status epilepticus depends upon the age of the animal, the timing of the first insult and subsequent formation of AMPA receptor subunit compositions within specific populations of hippocampal neurons.