期刊
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
卷 74, 期 3, 页码 273-285出版社
OXFORD UNIV PRESS INC
DOI: 10.1097/NEN.0000000000000172
关键词
Interferon regulatory factor-3; Microtubule-associated protein light chain; Toll-like receptor-3; White matter injury
资金
- UK Medical Research Council strategic award [P19381]
- Wellcome Trust [WT094823]
- Leducq Foundation
- Swedish Medical Research Council [VR 2012-3500]
- Wilhelm and Martina Lundgren Foundation
- Ahlen Foundation
- Frimurare Barnhus Foundation
- Byggmastare Olle Engqvist Foundation
- Brain Foundation [2013-0035]
- Governmental Grants for University Hospitals in Sweden [ALFGBG-137601]
- Department of Health via the National Institute for Health Research Comprehensive Biomedical Research Center
- King's College London
- King's College Hospital NHS Foundation Trust
- MRC [MC_U120088465, G0802853] Funding Source: UKRI
- Medical Research Council [MC_U120088465, G0802853] Funding Source: researchfish
Toll-like receptor-3 (TLR3) has been identified in a variety of intracellular structures (e. g. endosomes and endoplasmic reticulum); it detects viral molecular patterns and damage-associated molecular patterns. We hypothesized that, after white matter injury (WMI) has occurred, localization and activation of TLR3 are altered in gray matter structures in response to damage-associated molecular patterns and activated glia. Therefore, we investigated the subcellular localization of TLR3 and its downstream signaling pathway in postmortem brain sections from preterm infants with and without WMI (7 patients each). We assessed astroglia (glial fibrillary acidic protein-positive), microglia (ionized calcium-binding adaptor molecule-1-positive), and neuronal populations in 3 regions of the thalamus and in the posterior limb of the internal capsule and analyzed TLR3 messenger RNA and protein expression in the ventral lateral posterior thalamic region, an area associated with impaired motor function. We also assessed TLR3 colocalization with late endosomes (lysosome-associated membrane protein-1) and phagosomal compartments in this region. Glial fibrillary acidic protein, ionized calcium-binding adaptor molecule-1, and TLR3 immunoreactivity and messenger RNA expression were increased in cases with WMI compared with controls. In ventral lateral posterior neurons, TLR3 was colocalized with the endoplasmic reticulum and the autophagosome, suggesting that autophagy may be a stress response associated with WMI. Thus, alterations in TLR3 expression in WMI may be an underlying molecular mechanism associated with impaired development in preterm infants.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据