Altered expression of microtubule-associated protein 1B in cerebral cortical structures of pentylenetetrazole-treated rats.

Abstract

Using Northern blot, immunoblotting, immunocytochemistry, and in situ hybridization, we show that a single administration of the convulsant pentylenetetrazole leads to robust, long-term changes in microtubule-associated protein 1B and its mRNA, in the adult rat brain. The first increases in MAP1B mRNA were detected at 15 hr following pentylenetetrazole administration in the temporal (Te2) and perirhinal cortex followed by increases in microtubule-associated protein 1B immunoreactivity at 72 hr postseizure. In contrast, the levels of microtubule-associated protein 1B mRNA and protein in layers I-II of the retrosplenial and parietal cortex (Par2) declined visibly by 24 hr and 72 h, respectively, post-seizure. The changes included loss of staining in layers I-II and development of structures resembling "strings-of-beads" along the fibers of projection neurons of layer V. The levels of microtubule-associated protein 1B mRNA in the entorhinal cortex peaked at later times (72 h), especially in layers II-III, and returned to control levels by 10 days. Whereas the levels of microtubule-associated protein 1B immunoreactivity in the retrosplenial and parietal cortex recovered by 5-10 days, it persisted at high levels through day 35 in layer V of the temporal cortex (Te2), layers II-III of the perirhinal cortex and layers I-II of the lateral entorhinal cortex. These results indicate that seizure activity leads to long-term upregulation of genes coding for structural elements that are characteristic of the immature brain such as microtubule-associated protein 1B.