Glial Differences Between Naïve Withdrawal Seizure‐Prone and ‐Resistant Mice

Abstract

Withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice were bred in replicate (i.e., WSP-1 and WSP-2) to exhibit differences in handling-induced convulsion severity during ethanol withdrawal. We examined the role of the glutamatergic system in susceptibility to ethanol-withdrawal convulsions in naive mice by measuring the density of immunolabeling for several glutamate transporters and the glutamate-metabolizing enzyme, glutamine synthetase. The density of glial fibrillary acidic protein immunolabeling (a marker of glial structure) and cytochrome oxidase activity (a marker of neuronal activity) were also characterized in naive mice. We observed a significantly greater density of immunolabeling for the glial transporter, glutamate/aspartate transporter, in CA1 subfield of the hippocampus (CA1) of naive WSP-2 mice as compared to WSR-2 mice. No other significant differences were observed. However, as compared to WSR mice, naive WSP mice exhibited a trend toward (a) greater immunolabeling for the glial glutamate transporter, glutamate transporter-1, in CA3, (b) greater immunolabeling for glial-specific glutamate-metabolizing enzyme, glutamine synthetase, in CA1 (replicate-2 only), and (c) less immunolabeling for the glial structural protein, glial fibrillary acidic protein, in all brain regions tested. In contrast, no trends or significant differences in the labeling density for the neuronal transporter, excitatory amino acid carrier 1, or the neuronal activity marker, cytochrome oxidase, were observed between the selected lines. These data suggest that the glutamatergic system and glia may play a pivotal role in the increased susceptibility to handling-induced convulsions observed in WSP mice.