Genetically determined susceptibility to neurodegeneration is associated with expression of inflammatory genes.
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.
Swanberg
Maria
M
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, CMM, L8:04, Karolinska University Hospital Solna, SE-17176, Stockholm, Sweden. Maria.Swanberg@cmm.ki.se
Duvefelt
Kristina
K
Diez
Margarita
M
Hillert
Jan
J
Olsson
Tomas
T
Piehl
Fredrik
F
Lidman
Olle
O
D000818:Animals; D019771:Axotomy; D016923:Cell Death / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003627:Data Interpretation, Statistical; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D018960:Hyaluronan Receptors / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000235:genetics*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins; D009410:Nerve Degeneration / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000502:physiology; D025341:Principal Component Analysis; D051381:Rats; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
C490195:C1qbp protein, rat; D018076:DNA, Complementary; D018960:Hyaluronan Receptors; D024101:Mitochondrial Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1