Rapid disease development in scrapie-infected mice deficient for CD40 ligand.
The inhibition of CD40-CD40L interaction-mediated signalling was suggested as a therapeutic strategy for the treatment of Alzheimer's disease. Conversely, CD40-deficient neurons were reported to be more vulnerable to stress associated with ageing as well as nerve growth factor-beta and serum withdrawal. We studied the scrapie infection of CD40L-deficient (CD40L(-/-)) mice to see whether ablation of the CD40L gene would be beneficial or detrimental in this model of a neurodegenerative amyloidosis. CD40L(-/-) mice died on average 40 days earlier than wild-type control mice and exhibited a more pronounced vacuolation of the neuropil and an increased microglia activation. The experimental model indicates that a deficiency for CD40L is highly detrimental in prion diseases and reinforces the neuroprotective function of intact CD40-CD40L interactions. The stimulation of neuroprotective pathways may represent a possibility to delay therapeutically the disease onset in prion infections of the central nervous system.
Burwinkel
Michael
M
Project 'Neurodegenerative Diseases', Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Schwarz
Anja
A
Riemer
Constanze
C
Schultz
Julia
J
van Landeghem
Frank
F
Baier
Michael
M
D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000378:metabolism; D012608:Scrapie / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D015996:Survival Rate; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015415:Biomarkers; D019013:CD40 Antigens; D011328:Prions; D023201:CD40 Ligand; D005680:gamma-Aminobutyric Acid