Diazepam binding inhibitor overexpression in mice causes hydrocephalus, decreases plasticity in excitatory synapses and impairs hippocampus-dependent learning

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• 作者：Hanna Siiskonen ; Sanna Oikari ; Veli-Pekka Korhonen ; Asla Pitkä ; nen ; Vootele Voikar ; Mikko Kettunen ; Juhana Hakumä ; ki ; Tiina Wahlfors ; Raimo Pussinen ; Markku Penttonen ; et al.
• 刊名：Molecular and Cellular Neuroscience
• 出版年：2007
• 出版时间：February 2007
• 年：2007
• 卷：34
• 期：2
• 页码：199-208
• 全文大小：1157 K

文摘

Diazepam binding inhibitor (DBI) and its processing products are endogenous modulators of GABA_A 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 37× 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.