Anomalous expression of microtubule-associated protein 1B in the hippocampus and cortex of aged rats treated with pentylenetetrazole

The aim of the present study was to assess the age-dependent response of mi crotubule-associated protein 1B, a plasticity-associated protein deriving f rom a late gene, following administration of an epileptogenic stimulus. The effect of a single administration of the convulsant pentylenetetrazole on microtubule-associated protein 1B expression in the hippocampal formation a nd cortex of three-, 18- and 28-month-old rats was assessed using northern blot analysis, in situ hybridization and immunohistochemistry. In three-mon th-old rats, we detected initial increases in microtubule-associated protei n 1B messenger RNA at 15 h following pentylenetetrazole administration in t he granule cells of the dentate gyrus, in the CA3 region of the hippocampus and in layers II/III of the entorhinal cortex, and these reached a maximum at 44 h. However, in the hippocampus and cortex of 18-month-old rats, the peak occurred at 15 h, and in the brains of 28-month-old rats a blunted pea k was reached at 3 h. Pentylenetetrazole treatment in young rats resulted i n a robust induction of microtubule-associated protein 1B immunoreactivity in the granule cells of the dentate gyrus and in layers II/III of the entor hinal cortex, but also produced a large decrease in the retrosplenial corte x. However, following pentylenetetrazole treatment in older rats, the granu le cells of the dentate gyrus were nearly devoid of microtubule-associated protein 1B immunoreactivity, whereas the retrosplenial cortex showed no cha nges at all, and the entorhinal cortex had an expression pattern similar to that of young rats. Aberrant immunolabeling of microtubule-associated prot ein 1B occurred in cortical layer VI of the aged rats where, unlike in youn g rats, there was heavy staining of neuronal somata. These results suggest that the regulation of the plasticity-associated prot ein microtubule-associated protein 1B is altered in the ageing rat brain, w ith the peak of expression shifted to earlier times in 18-month-old rats an d blunted, variable increases at even earlier times in 28-month-old rats. ( C) 1999 IBRO. Published by Elsevier Science Ltd.