Amyloid plaque pathogenesis in 5XFAD mouse spinal cord: retrograde transneuronal modulation after peripheral nerve injur
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ORIGINAL ARTICLE
Amyloid plaque pathogenesis in 5XFAD mouse spinal cord: retrograde transneuronal modulation after peripheral nerve injury Jian-Ming Li • Zhi-Qin Xue • Si-Hao Deng • Xue-Gang Luo • Peter R. Patrylo • Gregory W. Rose Huaibin Cai • Yan Cai • Xiao-Xin Yan
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Received: 30 July 2012 / Revised: 14 September 2012 / Accepted: 26 September 2012 / Published online: 5 October 2012 Ó Springer Science+Business Media New York 2012
Abstract The spinal cord is composed of distinct neuronal groups with well-defined anatomic connections. In some transgenic (Tg) models of Alzheimer’s disease (AD), amyloid plaques develop in this structure, although the underlying cellular mechanism remains elusive. We attempted to explore the origin, evolution, and modulation of spinal b-amyloid (Ab) deposition using Tg mice harboring five familiar AD-related mutations (5XFAD) as an experiential model. Dystrophic neuritic elements with enhanced b-secretase-1 (BACE1) immunoreactivity (IR) appeared as early as 2 months of age, and increased with age up to 12 months examined in this study, mostly over the ventral horn (VH). Extracellular Ab IR emerged and developed during this same period, site-specifically co-existing with BACE1-labeled neurites often in the J.-M. Li Neuroscience Research Center, Changsha Medical University, Changsha 410219, Hunan, China J.-M. Li Z.-Q. Xue S.-H. Deng X.-G. Luo Y. Cai X.-X. Yan (&) Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha 410013, Hunan, China e-mail: [email protected] Z.-Q. Xue Department of Anatomy, Xinjiang Medical University, ¨ ru¨mqi 830011, Xinjiang, China U P. R. Patrylo G. W. Rose X.-X. Yan Center for Integrated Research in Cognitive and Neural Sciences, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA H. Cai Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
vicinity of large VH neurons that expressed the mutant human APP. The BACE1-labeled neurites almost invariably colocalized with b-amyloid precursor protein (APP) and synaptophysin, and frequently with the vesicular glutamate transporter-1 (VGLUT). Reduced IR for the neuronal-specific nuclear antigen (NeuN) occurred in the VH by 12 months of age. In 8-month-old animals surviving 6 months after a unilateral sciatic nerve transection, there were significant increases of Ab, BACE1, and VGLUT IR in the VN of the ipsilateral relative to contralateral lumbar spinal segments. These results suggest that extracellular Ab deposition in 5XFAD mouse spinal cord relates to a progressive and amyloidogenic synaptic pathology largely involving presynaptic axon terminals from projection neurons in the brain. Spinal neuritic plaque formation is enhanced after peripheral axotomy, suggesting a retrograde transneuronal modulation on pathogenesis. Keywords Alzheimer’s disease Amyloidogenesis BACE1 Neuritic dystrophy Synaptoplasticity
Introduction b-Amyloid (Ab) peptides are produced followi
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