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


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).


CONCLUSIONS
These results suggest that the up-regulation of BDNF/trkB pathway might be at least in part responsible for the epileptogenesis.
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, China.
Xiaohua
X
Hou
Xiaoran
X
Wang
Liming
L
Zhang
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D020813:Receptor, trkB / Q000378:metabolism*; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D014635:Valproic Acid; D020813:Receptor, trkB