Apolipoprotein E isoform-dependent dendritic recovery of hippocampal neurons following activation of innate immunity |
| |
Authors: | Izumi Maezawa Snjezana Zaja-Milatovic Dejan Milatovic Christina Stephen Izabela Sokal Nobuyo Maeda Thomas J Montine and Kathleen S Montine |
| |
Institution: | (1) Department of Pathology, University of Washington, Seattle, WA, USA;(2) Department of Pathology, University of North Carolina, Chapel Hill, NC, USA |
| |
Abstract: | Background Innate immune activation, including a role for cluster of differentiation 14/toll-like receptor 4 co-receptors (CD14/TLR-4)
co-receptors, has been implicated in paracrine damage to neurons in several neurodegenerative diseases that also display stratification
of risk or clinical outcome with the common alleles of the apolipoprotein E gene (APOE): APOE2, APOE3, and APOE4. Previously, we have shown that specific stimulation of CD14/TLR-4 with lipopolysaccharide (LPS) leads to greatest innate
immune response by primary microglial cultures from targeted replacement (TR) APOE4 mice and greatest p38MAPK-dependent paracrine
damage to neurons in mixed primary cultures and hippocampal slice cultures derived from TR APOE4 mice. In contrast, TR APOE2
astrocytes had the highest NF-kappaB activity and no neurotoxicity. Here we tested the hypothesis that direct activation of
CD14/TLR-4 in vivo would yield different amounts of paracrine damage to hippocampal sector CA1 pyramidal neurons in TR APOE mice. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|