Brain-derived neurotrophic factor delays hippocampal kindling in the rat.
Epileptic seizures increase the expression of brain-derived neurotrophic factor in the hippocampus. Since this neurotrophin exerts modulatory effects on neuronal excitability in this structure, it may play an important role in hippocampal epileptogenesis. This question was addressed by studying the effects of chronic infusions of recombinant brain-derived neurotrophic factor and brain-derived neurotrophic factor antisense in the hippocampus during the first seven days of hippocampal kindling. Infusion with brain-derived neurotrophic factor (6-24 microg/day) significantly delayed the progression of standard hippocampal kindling and strongly suppressed seizures induced by rapid hippocampal kindling. These suppressive effects were dose dependent, long lasting, not secondary to neuronal toxicity and specific to this neurotrophin, as nerve growth factor accelerated hippocampal kindling progression. They also appeared to be specific to the hippocampus, as infusion of brain-derived neurotrophic factor (48 microg/day) in the amygdala only resulted in a slight and transient delay of amygdala kindling. Conversely to the protective effects of exogenous brain-derived neurotrophic factor, chronic hippocampal infusion of antisense oligodeoxynucleotides (12 nmol/day), resulting in reduced expression of endogenous brain-derived neurotrophic factor in the hippocampus, aggravated seizures during hippocampal kindling. Taken together, our results lead us to suggest that the seizure-induced increase in brain-derived neurotrophic factor expression in the hippocampus may constitute an endogenous regulatory mechanism able to restrain hippocampal epileptogenesis.
Reibel
S
S
INSERM U398, Faculté de Médecine, Université Louis Pasteur, 11 rue Humann, 67085 Cedex, Strasbourg, France.
Larmet
Y
Y
Lê
B T
BT
Carnahan
J
J
Marescaux
C
C
Depaulis
A
A
D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology*; D007839:Functional Laterality; D006624:Hippocampus / Q000503:physiopathology*; D007150:Immunohistochemistry; D007696:Kindling, Neurologic; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D019208:Brain-Derived Neurotrophic Factor; D016376:Oligonucleotides, Antisense