Advanced

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

Swanberg, Maria LU ; Duvefelt, Kristina; Diez, Margarita; Hillert, Jan; Olsson, Tomas; Piehl, Fredrik and Lidman, Olle (2006) In Neurobiology of Disease 24(1). p.67-88
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
@article{713aecd1-10f3-434d-8c38-2f96714503e6,
  abstract     = {<p>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.</p>},
  author       = {Swanberg, Maria and Duvefelt, Kristina and Diez, Margarita and Hillert, Jan and Olsson, Tomas and Piehl, Fredrik and Lidman, Olle},
  issn         = {0969-9961},
  keyword      = {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},
  language     = {eng},
  number       = {1},
  pages        = {67--88},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Genetically determined susceptibility to neurodegeneration is associated with expression of inflammatory genes},
  url          = {http://dx.doi.org/10.1016/j.nbd.2006.05.016},
  volume       = {24},
  year         = {2006},
}