Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination.
CNS remyelination occurs more rapidly in young adult rats than in old rats. Since the inflammatory response initiated by demyelination is an important trigger for remyelination, we address whether ageing changes in remyelination are associated with changes in the inflammatory response. Using a toxin model of demyelination, where the inflammatory response largely comprises macrophages, we show that there is a delay in both recruitment and activation of OX-42+ and macrophage scavenger receptor B+ macrophages following demyelination in older rats (10-13 months) compared to young rats (8-10 weeks). This difference is associated with a slower onset of increased expression of several chemokine mRNAs. However, many inflammatory cytokines have similar mRNA expression patterns, with the exception of IL-1beta, IL-6 and TNF-alpha, which have prolonged expression in the older animals. Differences in IL-1beta mRNA expression, a cytokine specifically implicated in CNS remyelination, are not reflected in differences in protein expression detected by immunocytochemistry. These data relate the age-associated delay in remyelination efficiency to changes in the macrophage and inflammatory mediator response to demyelination.
Zhao
Chao
C
Cambridge Center for Brain Repair and Neuroregeneration Laboratory, Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
Li
Wen-Wu
WW
Franklin
Robin J M
RJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D039481:CD11b Antigen; D002452:Cell Count / Q000379:methods; D002490:Central Nervous System / Q000503:physiopathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D008244:Lysophosphatidylcholines / Q000633:toxicity; D008264:Macrophages / Q000502:physiology; D046228:Microarray Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013118:Spinal Cord Diseases / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D014118:Toxins, Biological / Q000633:toxicity
D039481:CD11b Antigen; D016207:Cytokines; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D014118:Toxins, Biological