Deletion of selenoprotein P results in impaired function of parvalbumin interneurons and alterations in fear learning and sensorimotor gating

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• 作者：M.W. Pitts ; ^{mwpitts@hawaii.edu} ; A.V. Raman ; A.C. Hashimoto ; C. Todorovic ; R.A. Nichols ; M.J. Berry
• 关键词：selenoprotein P ; apolipoprotein receptor 2 ; parvalbumin interneurons ; oxidative stress ; inferior colliculus
• 刊名：Neuroscience
• 出版年：2012
• 期刊代码：50_03064522
• 类别：neu
• 出版时间：19 April, 2012
• 卷：208
• 期：Complete
• 页码：58-68
• 文件大小：4463 K

摘要

One of the primary lines of defense against oxidative stress is the selenoprotein family, a class of proteins that contain selenium in the form of the 21st amino acid, selenocysteine. Within this class of proteins, selenoprotein P (Sepp1) is unique, as it contains multiple selenocysteine residues and is postulated to act in selenium transport. Recent findings have demonstrated that neuronal selenoprotein synthesis is required for the development of parvalbumin (PV)-interneurons, a class of GABAergic neurons involved in the synchronization of neural activity. To investigate the potential influence of Sepp1 on PV-interneurons, we first mapped the distribution of the Sepp1 receptor, ApoER2, and parvalbumin in the mouse brain. Our results indicate that ApoER2 is highly expressed on PV-interneurons in multiple brain regions. Next, to determine whether PV-interneuron populations are affected by Sepp1 deletion, we performed stereology on several brain regions in which we observed ApoER2 expression on PV-interneurons, comparing wild-type and Sepp1^鈭?鈭?/em> mice. We observed reduced numbers of PV-interneurons in the inferior colliculus of Sepp1^鈭?鈭?/em> mice, which corresponded with a regional increase in oxidative stress. Finally, as impaired PV-interneuron function has been implicated in several neuropsychiatric conditions, we performed multiple behavioral tests on Sepp1^鈭?鈭?/em> mice. Our behavioral results indicate that Sepp1^鈭?鈭?/em> mice have impairments in contextual fear extinction, latent inhibition, and sensorimotor gating. In sum, these findings demonstrate the important supporting role of Sepp1 on ApoER2-expressing PV-interneurons.