CD40L deletion delays neuronal death in a model of neurodegeneration due to mild impairment of oxidative metabolism.
Inflammatory/immune processes are important in the pathogenesis of neurodegenerative diseases. Thiamine deficiency (TD) models the region selective neuronal loss in brain that accompanies mild impairment of oxidative metabolism. TD induces well-defined alterations in neurons, microglia, astrocytes, and endothelial cells. To test the role of inflammatory/immune mechanisms in TD-induced neurodegeneration, the temporal profile of neurodegeneration was compared to the activation of CD68-positive microglia and ICAM-1-positive endothelial cells during TD in wild type mice and in CD40L-/- mice. CD40L-/- delayed the onset of TD-induced neuronal death as well as the activation of microglia and endothelial cells. The current results suggest that CD40L-mediated immune and inflammatory responses have a role in TD-induced neuronal death.
Ke
Zun-Ji
ZJ
Institute for Nutritional Sciences, SIBS, CAS, 294 Taiyuan Road, Shanghai 200031, PR China.
Calingasan
Noel Y
NY
Karuppagounder
Saravanan S
SS
DeGiorgio
Lorraine A
LA
Volpe
Bruce T
BT
Gibson
Gary E
GE
D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics*; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D017353:Gene Deletion; D007150:Immunohistochemistry / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology; D009474:Neurons / Q000502:physiology*; D009930:Organic Chemicals; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013832:Thiamine Deficiency / Q000150:complications* / Q000473:pathology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D023201:CD40 Ligand; D005452:Fluoresceins; D005456:Fluorescent Dyes; D018799:Intercellular Adhesion Molecule-1; D009930:Organic Chemicals; D010751:Phosphopyruvate Hydratase; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C435731:fluoro jade