Differences in the Early Inflammatory Responses to Toxin-Induced Demyelination Are Associated With the Age-Related Decline in CNS Remyelination

Neurobiol Aging. 2006 Sep;27(9):1298-307. doi: 10.1016/j.neurobiolaging.2005.06.008. Epub 2005 Jul 26.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • CD11b Antigen
  • Cell Count / methods
  • Central Nervous System / physiopathology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / complications
  • Demyelinating Diseases / physiopathology*
  • Disease Models, Animal
  • Female
  • Gene Expression / physiology
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Inflammation / etiology
  • Inflammation / physiopathology*
  • Lysophosphatidylcholines / toxicity
  • Macrophages / physiology
  • Microarray Analysis / methods
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Spinal Cord Diseases / chemically induced
  • Spinal Cord Diseases / complications
  • Spinal Cord Diseases / physiopathology
  • Toxins, Biological / toxicity

Substances

  • CD11b Antigen
  • Cytokines
  • Lysophosphatidylcholines
  • RNA, Messenger
  • Toxins, Biological