• Home
  • Search Results
  • Subcutaneous Administration of AMD3100 into Mice Models of Alzheimer's Disease Ameliorated Cognitive Impairment, Reduced Neuroinflammation, and Improved Pathophysiological Markers.

Subcutaneous Administration of AMD3100 into Mice Models of Alzheimer's Disease Ameliorated Cognitive Impairment, Reduced Neuroinflammation, and Improved Pathophysiological Markers.

Journal of Alzheimer's disease : JAD (2020-10-06)
Yuval Gavriel, Inna Rabinovich-Nikitin, Assaf Ezra, Becki Barbiro, Beka Solomon
ABSTRACT

Alzheimer's disease (AD), the prevalent dementia in the elderly, involves many related and interdependent pathologies that manifest simultaneously, leading to cognitive impairment and death. Amyloid-β (Aβ) accumulation in the brain triggers the onset of AD, accompanied by neuroinflammatory response and pathological changes. The CXCR4/CXCL12 (SDF1) axis is one of the major signal transduction cascades involved in the inflammation process and regulation of homing of hematopoietic stem cells (HSCs) within the bone marrow niche. Inhibition of the axis with AMD3100, a reversible antagonist of CXCR4 mobilizes endogenous HSCs from the bone marrow into the periphery, facilitating the recruitment of bone marrow-derived microglia-like cells into the brain, attenuates the neuroinflammation process that involves release of excitotoxic markers such as TNFα, intracellular Ca2 +, and glutamate and upregulates monocarboxylate transporter 1, the major L-lactate transporter in the brain. Herein, we investigate if administration of a combination of AMD3100 and L-lactate may have beneficial effects in the treatment of AD. We tested the feasibility of the combined treatment for short- and long-term efficacy for inducing endogenous stem cells' mobilization and attenuation of neuroinflammation in two distinct amyloid-β-induced AD mouse models. The combined treatment did not demonstrate any adverse effects on the mice, and resulted in a significant improvement in cognitive/memory functions, attenuated neuroinflammation, and alleviated AD pathologies compared to each treatment alone. This study showed AMD3100's beneficial effect in ameliorating AD pathogenesis, suggesting an alternative to the multistep procedures of transplantation of stem cells in the treatment of AD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium L-lactate, ≥99.0% (NT)
Sigma-Aldrich
Anti-α-Tubulin antibody, Mouse monoclonal, clone DM1A, purified from hybridoma cell culture
Sigma-Aldrich
AMD3100 octahydrochloride hydrate, ≥97% (NMR), solid
Sigma-Aldrich
Amyloid β-Protein Fragment 25-35, ≥97% (HPLC)
Sigma-Aldrich
Anti-ITGAM antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-phospho-APP (pThr668) antibody produced in rabbit, affinity isolated antibody, aqueous glycerol solution, 10 blots