Differential regulation of MAP2 and alphaCamKII expression in hippocampal neurones by forskolin and calcium ionophore treatment.
The genes encoding microtubule-associated protein 2 (MAP2), and the alpha subunit of calcium/calmodulin-dependent protein kinase II (alphaCaMKII), are members of a small number of genes whose expression is increased in hippocampal neurones during the intermediate phase of long-term potentiation (LTP)-a phase dependent on mRNA translation but not on gene transcription. However, the intracellular signalling pathways which mediate these increases in expression are largely unknown. Organotypic slice cultures of rat hippocampus were exposed to either forskolin (to elevate cAMP levels), A23187 (to increase intracellular Ca(2+) levels) or the corresponding vehicle. The levels of immunoreactive (ir-) MAP2 were increased 4 h after forskolin treatment, but were unaffected by A23187 treatment. Conversely, the levels of ir-alphaCaMKII were increased 4 h after A23187 treatment, but were unaffected by forskolin. The regulation of the expression of these proteins was the same in the CA3 region as in the CA1 and dentate gyrus of the hippocampus. While rapamycin reduced the basal levels of ir-MAP2, it did not affect the ability of either forskolin or A23187 to enhance ir-MAP2 or ir-alphaCaMKII levels. These results suggest that cAMP and Ca(2+) differentially modulate the expression of these two plasticity-related genes, and that translational enhancement via the mammalian target of rapamycin kinase is not involved in these effects.
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, West Medical Building, Glasgow G12 8QQ, UK.
K A
KA
Alier
B J
BJ
Morris
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology
D007166:Immunosuppressive Agents; D007476:Ionophores; D008869:Microtubule-Associated Proteins; D005576:Colforsin; D000001:Calcimycin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium; D020123:Sirolimus