Induction of brain-derived neurotrophic factor by convulsant drugs in the rat brain: involvement of region-specific voltage-dependent calcium channels

Citation
R. Katoh-semba et al., Induction of brain-derived neurotrophic factor by convulsant drugs in the rat brain: involvement of region-specific voltage-dependent calcium channels, J NEUROCHEM, 77(1), 2001, pp. 71-83
Citations number
55
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
0022-3042 → ACNP
Volume
77
Issue
1
Year of publication
2001
Pages
71 - 83
Database
ISI
SICI code
0022-3042(200104)77:1<71:IOBNFB>2.0.ZU;2-J
Abstract
A high level of hippocampal brain-derived neurotrophic factor (BDNF) in nor mally aged as compared with young rats suggests that it is important to mai ntain a considerable level of hippocampal BDNF during aging in order to kee p normal hippocampal functions. To elucidate possible mechanisms of endogen ous BDNF increase, changes in levels of BDNF were studied in the rat brain following systemic administration of various convulsant agents; excitotoxic glutamate agonists, NMDA, kainic acid and (+/-)-alpha -amino-3-hydroxy-5-m ethyl-isoxazole-4-propionic acid (AMPA); GABA receptor antagonists, picroto xin, pentylenetetrazole (PTZ) and lindane (gamma -hexachloro-cyclohexane); and L-type voltage-dependent calcium channel agonist, BAY-K 8644. Kainic ac id and AMPA, but not NMDA, caused remarkable increases in BDNF protein in t he rat hippocampus and entorhinal cortex. Picrotoxin, PTZ and lindane stimu lated BDNF production in the entorhinal cortex and also in the hippocampus of rats showing very severe convulsions. On the other hand, BAY-K 8644 trea tment increased BDNF levels in the neocortex and entorhinal cortex. Maximal levels of BDNF protein were observed at 12-24 h, 8-16 h and 6 h following administration of kainic acid, PTZ and BAY-K 8644, respectively. Kainic aci d stimulated BDNF synthesis in presynaptic hippocampal granule neurons, but not in postsynaptic neurons with its receptors, while PTZ and BAY-K 8644 p roduced the same effects in postsynaptic neurons in the entorhinal dorter t in granule neurons in the hippocampus) and in the whole cortex, respectivel y. Nifedipine inhibited almost completely BAY-K 8644, but not PTZ, effects. omega -Conotoxin GVIA and DCG-IV partially blocked kainic acid-induced enh ancement of BDNF, indicating involvement of L-type and N-type voltage-depen dent calcium channels, respectively. In addition; BDNF levels in the hippoc ampus of mice deficient in D-myo-inositol-1,4,5-triphosphate receptor gene were scarcely different from those in the same -region of controls, suggest ing little involvement of intracellular calcium increase through this recep tor; BAY-K 8644, but not kainic acid or PTZ, stimulated the phosphorylation of cyclic AMP responsive element binding protein. Our results indicate con vulsant-dependent stimulation of BDNF production and involvement of region- specific voltage-dependent calcium channels.