PMID- 14580953
OWN - NLM
STAT- MEDLINE
DCOM- 20040301
LR  - 20190712
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 121
IP  - 4
DP  - 2003
TI  - Persistent regional increases in brain-derived neurotrophic factor in the 
      flurothyl model of epileptogenesis are dependent upon the kindling status of the 
      animal.
PG  - 1031-45
AB  - Brain-derived neurotrophic factor (BDNF) appears to be both regulated by and a 
      regulator of epileptogenesis. In the flurothyl (HFE) model of kindling mice 
      exposed to successive flurothyl trials over 8 days express a rapid, long-lasting 
      reduction in generalized seizure threshold and a more slowly evolving change in 
      seizure phenotype in response to subsequent flurothyl exposure. The BDNF genotype 
      of particular mouse strains appears to influence the epileptogenic progression in 
      this model. Thus, we hypothesized that BDNF signaling pathways are altered by 
      flurothyl-induced seizures. Following HFE kindling, fully kindled (eight 
      seizures) adult male C57BI/6J mice had significantly elevated whole brain BDNF 
      levels through at least 28 days after their final seizure. Mice that received 
      only four HFE seizures (not kindled) had elevated BDNF levels, but only at 1 day 
      post-seizure (DPSz), while BDNF levels were not significantly altered in mice 
      receiving just one HFE seizure at any time point studied. Regional expression 
      patterns of BDNF in the hippocampus, hypothalamus, and frontal cortex were also 
      elevated by one DPSz and returned to control values by 14 DPSz in mice that 
      received four HFE seizures. No changes were seen in the cerebellum, striatum, or 
      piriform cortex. In contrast, fully kindled mice had significantly elevated BDNF 
      levels within the hippocampus, hypothalamus, neocortex, and striatum that 
      remained elevated through at least 14 DPSz, while levels were unchanged in the 
      cerebellum and piriform cortex. Regional results were confirmed using anti-BDNF 
      immunohistochemistry (IHC). Despite changes in BDNF levels following HFE 
      kindling, we were unable to demonstrate alterations either in full-length 
      tyrosine kinase receptor B (TrkB) expression (Western blot and IHC) or in 
      truncated TrkB (IHC) expression levels. Together, these data suggest a model of a 
      positive feedback loop involving seizure activity and seizure number and 
      persistently modified BDNF signaling pathways that influences seizure phenotypes 
      within the HFE kindling paradigm. Thus, long-term elevations in BDNF may be 
      responsible in part for epileptogenic processes and the development of human 
      refractory epilepsies.
FAU - Mhyre, T R
AU  - Mhyre TR
AD  - Strong Epilepsy Center, Department of Neurology, University of Rochester Medical 
      Center, Box 673, 601 Elmwood Avenue, Rochester, NY 14642, USA. 
      timothy_mhyre@urmc.rochester.edu
FAU - Applegate, C D
AU  - Applegate CD
LA  - eng
GR  - 5R01NS38607-02/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 9Z467FG2YK (Flurothyl)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Disease Models, Animal
MH  - Epilepsy/chemically induced/*metabolism/physiopathology
MH  - Flurothyl/pharmacology
MH  - Immunohistochemistry
MH  - Kindling, Neurologic/drug effects/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Neurological
MH  - Phenotype
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction/physiology
MH  - Up-Regulation/*physiology
EDAT- 2003/10/29 05:00
MHDA- 2004/03/03 05:00
CRDT- 2003/10/29 05:00
PHST- 2003/10/29 05:00 [pubmed]
PHST- 2004/03/03 05:00 [medline]
PHST- 2003/10/29 05:00 [entrez]
AID - S0306452203004755 [pii]
AID - 10.1016/s0306-4522(03)00475-5 [doi]
PST - ppublish
SO  - Neuroscience. 2003;121(4):1031-45. doi: 10.1016/s0306-4522(03)00475-5.