NEUROBIOLOGY OF AGING | 卷:44 |
Corticothalamic network dysfunction and behavioral deficits in a mouse model of Alzheimer's disease | |
Article | |
Hazra, Anupam1,2  Corbett, Brian F.1,2  You, Jason C.1,2  Aschmies, Suzan1,2  Zhao, Lijuan1,2  Li, Ke1,2  Lepore, Angelo C.1,2  Marsh, Eric D.3,4  Chin, Jeannie1,2,5  | |
[1] Thomas Jefferson Univ, Dept Neurosci, Philadelphia, PA 19107 USA | |
[2] Thomas Jefferson Univ, Farber Inst Neurosci, Philadelphia, PA 19107 USA | |
[3] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA | |
[4] Univ Penn, Childrens Hosp Philadelphia, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA | |
[5] Baylor Coll Med, Dept Neurosci, Memory & Brain Res Ctr, 1 Baylor Plaza,S707, Houston, TX 77030 USA | |
关键词: Alzheimer's disease; Seizure; Epilepsy; Corticothalamic; Amyloid precursor protein; Sleep fragmentation; Reticular thalamic nucleus (nRT); | |
DOI : 10.1016/j.neurobiolaging.2016.04.016 | |
来源: Elsevier | |
【 摘 要 】
Alzheimer's disease is associated with cognitive decline and seizures. Growing evidence indicates that seizures contribute to cognitive deficits early in disease, but how they develop and impact cognition are unclear. To investigate potential mechanisms, we studied a mouse model that overexpresses mutant human amyloid precursor protein with high levels of amyloid beta (Ab). These mice develop generalized epileptiform activity, including nonconvulsive seizures, consistent with alterations in corticothalamic network activity. Amyloid precursor protein mice exhibited reduced activity marker expression in the reticular thalamic nucleus, a key inhibitory regulatory nucleus, and increased activity marker expression in downstream thalamic relay targets that project to cortex and limbic structures. Slice recordings revealed impaired cortical inputs to the reticular thalamic nucleus that may contribute to corticothalamic dysfunction. These results are consistent with our findings of impaired sleep maintenance in amyloid precursor protein mice. Finally, the severity of sleep impairments predicted the severity of deficits in Morris water maze, suggesting corticothalamic dysfunction may relate to hippocampal dysfunction, and may be a pathophysiological mechanism underlying multiple behavioral and cognitive alterations in Alzheimer's disease. (C) 2016 Elsevier Inc. All rights reserved.
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