Genetically determined susceptibility to neurodegeneration is associated with expression of inflammatory genes

Research output: Contribution to journalArticle

Abstract

Axonal damage, a core feature of neurological diseases, induces a retrograde reaction in neurons and surrounding glia. We determined transcriptional profiles of this reaction using Affymetrix oligonucleotide arrays. Gene expression was examined in spinal cord tissue prior to injury and following ventral root avulsion in two inbred rat strains, where the degree of neurodegeneration differs. Stringent statistical analysis revealed 278 regulated genes, whereof 245 were regulated by the injury and 68 differed between strains. Principal component analysis disclosed a common injury response pattern significantly modified by genetic background. Notably, inflammatory genes comprised the largest group of genes induced by injury and these transcripts prevailed in the strain most susceptible to neurodegeneration. In addition, levels of the strain regulated genes C1qb and Timp1 correlated with degree of neurodegeneration in a cohort of genetically heterogeneous animals. These results suggest a link between the inflammatory response elicited by nerve injury and subsequent neurodegeneration.

Details

Authors
  • Maria Swanberg
  • Kristina Duvefelt
  • Margarita Diez
  • Jan Hillert
  • Tomas Olsson
  • Fredrik Piehl
  • Olle Lidman
External organisations
  • Karolinska Institutet
Research areas and keywords

Keywords

  • Animals, Antigens, CD44, Axotomy, Cell Death, Cell Proliferation, Cell Survival, Cytoskeleton, DNA, Complementary, Data Interpretation, Statistical, Extracellular Matrix, Gene Expression, Gene Expression Regulation, Immunohistochemistry, In Situ Hybridization, Inflammation, Lysosomes, Male, Mitochondrial Proteins, Nerve Degeneration, Neurons, Oligonucleotide Array Sequence Analysis, Oxidative Stress, Principal Component Analysis, Rats, Rats, Inbred Strains, Reverse Transcriptase Polymerase Chain Reaction, Synaptic Transmission, Tissue Inhibitor of Metalloproteinase-1, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)67-88
Number of pages22
JournalNeurobiology of Disease
Volume24
Issue number1
Publication statusPublished - 2006
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes