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Riluzole enhances expression of brain‐derived neurotrophic factor with consequent proliferation of granule precursor cells in the rat hippocampus
Author(s) -
Katoh RitsukoSemba,
Asano Tomiko,
Ueda Hiroshi,
Morishita Rika,
Takeuchi Ikuo K.,
Inaguma Yutaka,
Kato Kanefusa
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0143fje
Subject(s) - dentate gyrus , hippocampal formation , neurogenesis , neurotrophic factors , neuroscience , riluzole , brain derived neurotrophic factor , granule cell , neuroprotection , neurotrophin , chemistry , hippocampus , biology , medicine , amyotrophic lateral sclerosis , receptor , disease
The dentate gyrus of the hippocampus, generating new cells throughout life, is essential for normal recognition memory performance. Reduction of brain‐derived neurotrophic factor (BDNF) in this structure impairs its functions. To elucidate the association between BDNF levels and hippocampal neurogenesis, we first conducted a search for compounds that stimulate endogenous BDNF production in hippocampal granule neurons. Among ion channel modulators tested, riluzole, a neuroprotective agent with anticonvulsant properties that is approved for treatment of amyotrophic lateral sclerosis, was highly effective as a single dose by an intraperitoneal injection, causing a rise in BDNF localized in dentate granule neurons, the hilus, and the stratum radiatum of the CA3 region. Repeated, but not single, injections resulted in prolonged elevation of hippocampal BDNF and were associated with increased numbers of newly generated cells in the granule cell layer. This appeared due to promoted proliferation rather than survival of precursor cells, many of which differentiated into neurons. Intraventricular administration of BDNF‐specific antibodies blocked such riluzole effects, suggesting that BDNF increase is necessary for the promotion of precursor proliferation. Our results suggest the basis for a new strategy for treatment of memory dysfunction.