Merck
  • Home
  • Search Results
  • Amyloid plaque pathogenesis in 5XFAD mouse spinal cord: retrograde transneuronal modulation after peripheral nerve injury.

Amyloid plaque pathogenesis in 5XFAD mouse spinal cord: retrograde transneuronal modulation after peripheral nerve injury.

Neurotoxicity research (2012-10-12)
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
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 β-amyloid (Aβ) deposition using Tg mice harboring five familiar AD-related mutations (5XFAD) as an experiential model. Dystrophic neuritic elements with enhanced β-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 Aβ IR emerged and developed during this same period, site-specifically co-existing with BACE1-labeled neurites often in the vicinity of large VH neurons that expressed the mutant human APP. The BACE1-labeled neurites almost invariably colocalized with β-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 Aβ, BACE1, and VGLUT IR in the VN of the ipsilateral relative to contralateral lumbar spinal segments. These results suggest that extracellular Aβ 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-Parvalbumin antibody produced in mouse, clone PARV-19, ascites fluid
Sigma-Aldrich
Anti-Synaptophysin Antibody, clone SP15, ascites fluid, clone SP15, Chemicon®
Sigma-Aldrich
Anti-MAP2 antibody, Mouse Monoclonal, clone HM-2, purified from hybridoma cell culture
Sigma-Aldrich
Monoclonal Anti-Growth Associated Protein-43 antibody produced in mouse, clone GAP-7B10, ascites fluid
Sigma-Aldrich
Anti-Glial Fibrillary Acidic Protein antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide 2′-phosphate reduced tetrasodium salt hydrate, ≥97% (HPLC)
Sigma-Aldrich
Anti-GAD67 Antibody, clone 1G10.2, clone 1G10.2, Chemicon®, from mouse