Hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure susceptibility.
Disrupted ontogeny of forebrain inhibitory interneurons leads to neurological disorders, including epilepsy. Adult mice lacking the urokinase plasminogen activator receptor (Plaur) have decreased numbers of neocortical GABAergic interneurons and spontaneous seizures, attributed to a reduction of hepatocyte growth factor/scatter factor (HGF/SF). We report that by increasing endogenous HGF/SF concentration in the postnatal Plaur null mouse brain maintains the interneuron populations in the adult, reverses the seizure behavior and stabilizes the spontaneous electroencephalogram activity. The perinatal intervention provides a pathway to reverse potential birth defects and ameliorate seizures in the adult.
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Mihyun H
MH
Bae
Gregory B
GB
Bissonette
Wendy M
WM
Mars
George K
GK
Michalopoulos
Cristian L
CL
Achim
Didier A
DA
Depireux
Elizabeth M
EM
Powell
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D004198:Disease Susceptibility / Q000378:metabolism*; D004569:Electroencephalography / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009433:Neural Inhibition / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D010433:Pentylenetetrazole; D011930:Reaction Time / Q000187:drug effects; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D010320:Parvalbumins; C524899:Plaur protein, mouse; D055293:Receptors, Urokinase Plasminogen Activator; D005680:gamma-Aminobutyric Acid; D017228:Hepatocyte Growth Factor; D010433:Pentylenetetrazole