Increased expression of microtubule-associated protein 1B in the hippocampus, subiculum, and perforant path of rats treated with a high dose of pentylenetetrazole.
A single administration of the convulsant pentylenetetrazole (PTZ) initiates a complex pattern of long-term changes in microtubule-associated protein 1B (MAP1B) expression across the hippocampal formation. Using Northern blot and in situ hybridization we show that the first increases in MAP1B mRNA were detected at 15 h following PTZ administration in the granule cells of the dentate gyrus and CA3 region of the hippocampus and reached a maximum at 44 h. The levels of MAP1B mRNA in the subiculum peaked at later times (5 days). At 72 h MAP1B immunoreactivity was mainly localized in the granule-cell bodies and dentate inner and midmolecular layer as well as in neuronal cell bodies and the stratum lucidum, including the mossy fiber pathway of the CA3 region. By 5-10 days the levels of MAP1B in the pyramidal cells in the CA3 region decreased to very low levels; rather, heavy staining of interneuron-like cells and "strings-of-bead" structures all over the hippocampus and at the stratum oriens/alveus border were seen. The levels of MAP1B in the hippocampus returned to control levels by 20 days after PTZ administration. MAP1B immunoreactivity in the alvear path was also evident at 5 days postinjection at the CA1/alveus border. The intensity of MAP1B staining increased gradually in the perforant path starting at 72 h and persisted at high levels until day 35. Our studies show that (i) MAP1B is a temporal and regional marker for rapid and acute epileptic seizures and (ii) long-term increases in MAP1B in the perforant path might play a role in PTZ-induced seizures.
Popa-Wagner
A
A
Department of Neurology, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
Fischer
B
B
Schmoll
H
H
Platt
D
D
Kessler
C
C
D000818:Animals; D015415:Biomarkers; D015152:Blotting, Northern; D015153:Blotting, Western; D003292:Convulsants / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010433:Pentylenetetrazole / Q000494:pharmacology*; D019580:Perforant Pathway / Q000187:drug effects* / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D003292:Convulsants; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C085284:microtubule-associated protein 1B; D010433:Pentylenetetrazole