Beta-amyloid cortical deposits are accompanied by the loss of serotonergic neurons in the dog.
Dogs may naturally suffer an age-related cognitive impairment that has aroused a great deal of interest, even beyond the field of the veterinary clinic. This canine senile dementia reproduces several key aspects of Alzheimer's disease (AD), including the presence of beta-amyloid (A beta) deposits in the cerebral cortex, neurodegeneration, and learning and memory impairments. In the present study, we have used unbiased stereological procedures to estimate the number of the dorsal and median raphe nuclei (DRN and MRN, respectively) serotonergic neurons immunolabeled with an anti-tryptophan hydroxylase (TrH) monoclonal antibody in young and aged dogs without A beta cortical deposits and in aged dogs with A beta cortical deposits. The estimated total number of TrH-labeled neurons (mean +/- SD) was 94,790 +/- 26,341 for the DRN and 40,404 +/- 8,692 for the MRN. The statistical analyses revealed that aged dogs with A beta cortical pathology had 33% fewer serotonergic neurons in the DRN and MRN than aged dogs without A beta cortical deposits (108,043 +/- 18,800 vs. 162,242 +/- 39,942, respectively; P = 0.01). In contrast, no significant variations were found between young and aged dogs without A beta cortical deposits. These results suggest that degeneration of the serotonergic neurons could be involved in the cognitive damage that accompanies A beta cortical pathology in the dog and reinforce the use of the canine model for exploring the potential mechanisms linking the cortical A beta pathology and serotonergic neurodegeneration that occurs during the course of AD.
Bernedo
Vanessa
V
Departamento de Ciencias Clínicas Veterinarias, Universidad de Santiago de Compostela, Facultad de Veterinaria de Lugo, 27002 Lugo, Spain.
Insua
Daniel
D
Suárez
María-Luisa
ML
Santamarina
Germán
G
Sarasa
Manuel
M
Pesini
Pedro
P
D000375:Aging; D000544:Alzheimer Disease / Q000473:pathology / Q000662:veterinary*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000662:veterinary*; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D011903:Raphe Nuclei / Q000378:metabolism / Q000473:pathology*; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D016229:Amyloid beta-Peptides; D012701:Serotonin; D014365:Tryptophan Hydroxylase