Dogs with canine counterpart of Alzheimer's disease lose noradrenergic neurons.
Degeneration of noradrenergic neurons in the locus ceruleus is a well-described feature of Alzheimer's disease (AD). In spite of extensive utilization of the dog as a model for human degenerative diseases, there is no data on the response to aging of the noradrenergic system in dogs. We have used modern unbiased stereology to estimate the total number of A6-A7 noradrenergic neurons in normal, aged dogs and dogs with the canine counterpart of AD. In small-breed dogs with no cognitive impairments, the total mean number of tyrosine hydroxylase immunolabeled A6-A7 neurons was 17,228+/-1655, with no differences between young and aged dogs. In contrast, aged dogs with cognitive impairments exhibited a significant reduction in the total number of A6-A7 neurons (13,487+/-1374; P=0.001). Additionally, we found a negative correlation between the number of A6-A7 neurons and the extent of beta-amyloid deposits in the prefrontal cortex. These results suggest that the canine model could be useful in exploring the potential benefits of noradrenergic drugs for the treatment of AD.
Departamento de Ciencias Clínicas Veterinarias, Facultad de Veterinaria de Lugo, Universidad de Santiago de Compostela, 27002 Lugo, Spain.
Daniel
D
Insua
María-Luisa
ML
Suárez
Germán
G
Santamarina
Manuel
M
Sarasa
Pedro
P
Pesini
D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D046028:Canidae / Q000033:anatomy & histology / Q000378:metabolism; D002452:Cell Count; D003072:Cognition Disorders / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009638:Norepinephrine / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013045:Species Specificity; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
D015415:Biomarkers; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine