Conditional downregulation of brain- derived neurotrophic factor and tyrosine kinase receptor B blocks epileptogenesis in the human temporal lobe epilepsy hippocampus

Neurol India. 2010 Jan-Feb;58(1):29-34. doi: 10.4103/0028-3886.60392.

Abstract

Background: Brain-derived neurotrophic factor (BDNF) has been implicated as a potential therapeutic target in temporal lobe epilepsy (TLE). However, whether BDNF exerts an epileptogenic or antiepileptogenic function remains controversial.

Materials and methods: BDNF/tyrosine kinase receptor B (trkB) expression levels were comparatively assessed in the hippocampal tissue of TLE patients with (HS group) and without hippocampal sclerosis (non-HS group) as well as from non-epileptic controls.

Results: Immunohistochemistry and immunoblot analysis revealed a marked increase in BDNF/trkB expression in the dentate gyrus and CA3 regions of HS and non-HS groups. The lack of any differences in expression levels was observed between HS and non-HS patients. Meanwhile, treatment with VPA (Valproic acid, anti-epileptic drug) resulted in a significant down-regulation of BDNF/trkB protein expression in sclerotic and non-sclerotic hippocampus (P < 0.001). In contrast, no marked change was noticed in VPA-untreated and OA-treated groups (sodium octanoate).

Conclusion: These results suggest that the up-regulation of BDNF/trkB pathway might be at least in part responsible for the epileptogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Down-Regulation / drug effects
  • Down-Regulation / physiology*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Epilepsy, Temporal Lobe / drug therapy
  • Epilepsy, Temporal Lobe / pathology*
  • Epilepsy, Temporal Lobe / physiopathology
  • Female
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Humans
  • Male
  • Receptor, trkB / metabolism*
  • Time Factors
  • Valproic Acid / pharmacology
  • Valproic Acid / therapeutic use
  • Young Adult

Substances

  • Brain-Derived Neurotrophic Factor
  • Enzyme Inhibitors
  • Valproic Acid
  • Receptor, trkB