title: Diazepam binding inhibitor overexpression in mice causes hydrocephalus, decreases plasticity in excitatory synapses and impairs hippocampus-dependent learning.
abstract: Diazepam binding inhibitor (DBI) and its processing products are endogenous modulators of GABAA and linked to various brain disorders ranging from anxiety and drug dependence to epilepsy. To investigate the physiological role of endogenously expressed DBI in the brain we created a transgenic mouse line overexpressing DBI gene. Transgenic mice had a 37x increased protein expression and immunohistochemistry showed excessive glial expression in the infragranular region of the dentate gyrus. Transgenic animals had significantly larger lateral ventricles and decreased plasticity of excitatory synapses without affecting either inhibitory or excitatory synaptic transmission. In behavioral tests transgenic animals had no differences in motor and exploratory activity, yet impaired hippocampus-dependent learning and memory. Overexpression did not cause anxiety or proconflict behavior, nor influenced kainic acid or pentylenetetrazole induced seizure activity. Our transgenic mouse line demonstrates that endogenously overexpressed DBI impairs hippocampus-dependent learning without anxiety or proconflict behavior.
authors.affiliation: Department of Biotechnology/Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Siiskonen
authors.forename: Sanna
authors.initials: S
authors.lastname: Oikari
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Korhonen
authors.forename: Asla
authors.initials: A
authors.lastname: Pitkänen
authors.forename: Vootele
authors.initials: V
authors.lastname: Voikar
authors.forename: Mikko
authors.initials: M
authors.lastname: Kettunen
authors.forename: Juhana
authors.initials: J
authors.lastname: Hakumäki
authors.forename: Tiina
authors.initials: T
authors.lastname: Wahlfors
authors.forename: Raimo
authors.initials: R
authors.lastname: Pussinen
authors.forename: Markku
authors.initials: M
authors.lastname: Penttonen
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Kiehne
authors.forename: Selma K
authors.initials: SK
authors.lastname: Kaasinen
authors.forename: Leena
authors.initials: L
authors.lastname: Alhonen
authors.forename: Juhani
authors.initials: J
authors.lastname: Jänne
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herzig
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006849:Hydrocephalus / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D007859:Learning Disabilities / Q000235:genetics* / Q000473:pathology; D017774:Long-Term Potentiation / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011930:Reaction Time / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*
chemical_list: D026261:Diazepam Binding Inhibitor; D010751:Phosphopyruvate Hydratase