PMID- 10999534
OWN - NLM
STAT- MEDLINE
DCOM- 20001017
LR  - 20190813
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 41 Suppl 6
DP  - 2000
TI  - Endogenous control of hippocampal epileptogenesis: a molecular cascade involving 
      brain-derived neurotrophic factor and neuropeptide Y.
PG  - S127-33
AB  - PURPOSE: Seizures increase the expression of brain-derived neurotrophic factor 
      (BDNF) in the hippocampus. Because this neurotrophin exerts modulatory effects on 
      hippocampal neuronal excitability, it may play an important role in 
      epileptogenesis initiated in this structure. Moreover BDNF is known to regulate 
      the expression of neuropeptide Y (NPY), which displays modulatory properties on 
      seizure activity. This suggests that the effects of BDNF on epileptogenesis may 
      be mediated by NPY. METHODS: Adult male rats received a 7-day chronic 
      intrahippocampal infusion of BDNF, BDNF antisense oligodeoxynucleotides, NPY, or 
      anti-NPY immunoglobulin G during kindling of the hippocampus. The long-term 
      regulation of NPY expression by BDNF was also studied by immunohistochemistry and 
      radioimmunoassay. RESULTS: BDNF applied during the first week of hippocampal 
      stimulation significantly delayed the progression of kindling, an effect that 
      outlasted the end of the infusion by at least 7 days. Conversely, infusion of 
      BDNF antisense oligodeoxynucleotides to reduce the expression of endogenous BDNF 
      in the hippocampus aggravated the electroencephalographic expression of seizures. 
      Chronic infusion of BDNF increased the expression of NPY in the hippocampus, with 
      a time course similar to that of the protective effect of the neurotrophin on 
      kindling. Finally, chronic infusion of NPY in the hippocampus delayed the 
      progression of hippocampal kindling, whereas anti-NPY antibodies had an 
      aggravating effect. CONCLUSIONS: Our results suggest that the seizure-induced 
      increase in BDNF expression in the hippocampus may constitute an endogenous 
      protective mechanism able to counteract hippocampal epileptogenesis. This 
      protective effect appears to be mediated at least in part through the regulation 
      of NPY expression.
FAU - Reibel, S
AU  - Reibel S
AD  - Institut National de la Sante et de la Recherche Medicale U398, Faculte de 
      Medecine, Strasbourg, France. foisset@wanadoo.fr
FAU - Larmet, Y
AU  - Larmet Y
FAU - Carnahan, J
AU  - Carnahan J
FAU - Marescaux, C
AU  - Marescaux C
FAU - Depaulis, A
AU  - Depaulis A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuropeptide Y)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology/*physiology
MH  - Epilepsy/*physiopathology
MH  - Hippocampus/*physiopathology
MH  - Immunohistochemistry
MH  - Kindling, Neurologic/drug effects/*physiology
MH  - Male
MH  - Neuronal Plasticity
MH  - Neuropeptide Y/pharmacology/*physiology
MH  - Radioimmunoassay
MH  - Rats
EDAT- 2000/09/22 11:00
MHDA- 2000/10/21 11:01
CRDT- 2000/09/22 11:00
PHST- 2000/09/22 11:00 [pubmed]
PHST- 2000/10/21 11:01 [medline]
PHST- 2000/09/22 11:00 [entrez]
AID - 10.1111/j.1528-1157.2000.tb01571.x [doi]
PST - ppublish
SO  - Epilepsia. 2000;41 Suppl 6:S127-33. doi: 10.1111/j.1528-1157.2000.tb01571.x.