Receptor for AGE (RAGE) Signal Transduction in Amyotrophic Lateral Sclerosis: In Vivo Imaging and Novel Therapeutic Approaches
Abstract
(1) We tested expression patterns of RAGE in the SODG93A vs. wild-type mouse spinal cord. Active phagocytic CD68-positive SOD1G93A microglia express RAGE in the ventral horn of the spinal cord by the end-stages of the disease while microglia residing in the less affected white matter have less overlap with RAGE labeling. Only a few P2Y12 positive microglia (homeostasis marker) overlap with RAGE labeling and this remains relatively unchanged until P2Y12 positive cells disappear, suggesting that it is the active phagocytic microglia that display increased levels of RAGE. RAGE labels many neurons within the spinal cord throughout the disease, however, the overlap of total RAGE and MAP2 decreases by the end-stages, in parallel with increasing neuronal death. Initially, few astrocytes labeled by GFAP overlap with RAGE labeling, however, as astrocytes become increasingly prevalent in the ventral horn in the late stages of disease, there is increased overlap with RAGE labeling. (2) We generated the microglia RAGE modulated mice and their controls in the SOD1G93A background and are completing studies to understand the impact on life span and pathology. (3) We showed that the small molecule antagonist of RAGE is blood-brain barrier permeable; this will be tested in SOD1G93A mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2018
- Accession Number
- AD1060278
Entities
People
- Ann M. Schmidt
Organizations
- Grossman School of Medicine