Genetic dissection of neurodegeneration and CNS inflammation

Research output: Contribution to journalArticle

Abstract

Inflammation and neurodegeneration characterize multiple sclerosis, as well as many other diseases of the central nervous system (CNS). The understanding of the molecular pathways that regulate these processes is of fundamental importance for the development of new therapies. Nerve lesions paradigms in animals can serve as important tools to dissect central features of human CNS disease and by using these models certain key regulators have also been identified. However, our knowledge of how aspects of neurodegeneration and CNS inflammation are regulated on a genomic level is very limited. Such knowledge may help to unravel disease mechanisms. By using a standardized nerve trauma model, ventral root avulsion (VRA), in a series of inbred rat strains we here demonstrate a potent genetic regulation of the degree of neuron death and glial activation. Genome wide mapping of these phenotypes in experimental rat strain crosses identifies several quantitative trait loci (QTLs) controlling nerve lesion-induced nerve cell death, local T cell accumulation and expression of MHC class II on microglia. This approach may lead to the identification of evolutionary conserved genetic polymorphisms in key controlling genes, which can serve as prime candidates for association studies in several human CNS diseases.

Details

Authors
External organisations
  • Karolinska Institutet
Research areas and keywords

Keywords

  • Animals, Central Nervous System Diseases, Chromosome Mapping, Crosses, Genetic, Disease Models, Animal, Humans, Inflammation, Models, Biological, Neurodegenerative Diseases, Neuroglia, Journal Article, Review
Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalJournal of the Neurological Sciences
Volume233
Issue number1-2
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes