title: BDNF modifies hippocampal KCC2 and NKCC1 expression in a temporal lobe epilepsy model.
abstract: Excitatory GABA actions, induced by altered expression of chloride transporters (KCC2/NKCC1), can contribute to seizure generation in temporal lobe epilepsy. In the present study, we evaluated whether BDNF administration can affect KCC2/NKCC1 expression, ictogenesis and behavioral alterations in this paradigm. Status epilepticus was induced in male rats with pilocarpine, followed by a treatment of either a single high dose or multiple injections of BDNF during the latent phase of temporal lobe epilepsy. Chloride transporters expression, spontaneous recurrent seizures, and hyperexcitability post-seizural behaviors were evaluated after treatment. NKCC1 protein expression was markedly upregulated, whereas that of KCC2 was significantly downregulated in epileptic hippocampi compared to intact controls. Application of BDNF (both single high dose and multiple injections) increased KCC2 expression in epileptic hippocampi, while NKCC1 expression was downregulated exclusively by the single high dose injection of BDNF. Development of spontaneous recurrent seizures was delayed but not prevented by the treatment, and hyperexcitability behaviors were ameliorated for a short period of time. To prevent GABA-A mediated depolarization and design appropriate treatment strategies for temporal lobe epilepsy, chloride transporters can be considered as a target. Future studies are warranted to investigate any possible therapeutic effects of BDNF via altering chloride transporters expression.
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, mt.joghataei@yahoo.com.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Eftekhari
authors.forename: Soraya
authors.initials: S
authors.lastname: Mehrabi
authors.forename: Mansooreh
authors.initials: M
authors.lastname: Soleimani
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Hassanzadeh
authors.forename: Amene
authors.initials: A
authors.lastname: Shahrokhi
authors.forename: Hossein
authors.initials: H
authors.lastname: Mostafavi
authors.forename: Parisa
authors.initials: P
authors.lastname: Hayat
authors.forename: Mahmood
authors.initials: M
authors.lastname: Barati
authors.forename: Hajar
authors.initials: H
authors.lastname: Mehdizadeh
authors.forename: Reza
authors.initials: R
authors.lastname: Rahmanzadeh
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Hadjighassem
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Joghataei
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010862:Pilocarpine / Q000494:pharmacology; D017208:Rats, Wistar; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D010862:Pilocarpine; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters