Activation of p38 mitogen-activated protein kinase is required for in vivo brain-derived neurotrophic factor production in the rat hippocampus
| Autor: | Y. Takahashi, H. Yamada, Satoshi Ichisaka, Kanefusa Kato, Masako Tsuzuki, N. Miyazaki, Yoshio Hata, Satoko Kitajima, Ritsuko Katoh-Semba, R. Kaneko |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Kainic acid Pyridines AMPA receptor Tropomyosin receptor kinase B Adenosine A1 Receptor Antagonists Biology Hippocampus p38 Mitogen-Activated Protein Kinases Rats Sprague-Dawley chemistry.chemical_compound Calcium Channels N-Type Neurotrophic factors Internal medicine medicine Animals Enzyme Inhibitors Anisomycin Neurons Protein Synthesis Inhibitors Brain-derived neurotrophic factor Riluzole Voltage-dependent calcium channel Receptor Adenosine A1 Brain-Derived Neurotrophic Factor General Neuroscience Imidazoles Calcium Channel Blockers Adenosine A1 Receptor Agonists Rats Up-Regulation Enzyme Activation Endocrinology nervous system chemistry Excitatory Amino Acid Antagonists medicine.drug |
| Zdroj: | Neuroscience. 163:352-361 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2009.06.011 |
| Popis: | Several lines of evidence strongly suggest that brain-derived neurotrophic factor (BDNF) is associated with the formation, storage and recall of memory in the hippocampus and that it is important to maintain a considerable level of hippocampal BDNF in order to keep normal functions. BDNF can be synthesized in an activity-dependent manner. In fact, kainic acid or AMPA enhances BDNF levels in hippocampal granule neurons. However, the mechanisms of BDNF production are largely unclear. Recently, we have found that riluzole, which blocks voltage-gated sodium channels and thereby reduces glutamate release, actually strengthens immunoreactivity of BDNF in hippocampal granule neurons of rats. Therefore, we examined the riluzole-activated signaling pathways for BDNF production. Riluzole increased levels of phospho-p38 mitogen-activated protein kinase (p38 MAPK), as well as BDNF levels. Inhibition of p38 MAPK by SB203580 reduced riluzole effects, while activation of p38 MAPK by anisomycin increased levels of BDNF, suggesting that p38 MAPK can mediate BDNF production. Riluzole-induced elevation of phospho-activating transcription factor-2, a transcription factor downstream of p38 MAPK, was also observed. A blocker of N-type voltage-gated calcium channels reduced the effects of riluzole on BDNF production and p38 MAPK activation. We also examined a possible involvement of the adenosine A1 receptor in BDNF production because riluzole can influence ecto-nucleotide levels. An A1 receptor agonist inhibited riluzole-induced elevation of BDNF levels, whereas an antagonist not only increased levels of BDNF and active p38 MAPK but also augmented riluzole effects. These results indicate that, in the rat hippocampus, there is an in vivo signaling pathway for BDNF synthesis mediated by p38 MAPK, and that N-type voltage-gated calcium channels and/or adenosine A1 receptors contribute to p38 MAPK activation. |
| Databáze: | OpenAIRE |
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