Gamma-aminobutyric acidergic interneuron vulnerability to aging in canine prefrontal cortex.
The aged dog is considered a promising model for examining molecular and cellular processes involved in a variety of human neurological disorders. By using the canine counterpart of senile dementia of the Alzheimer's type (ccSDAT), we investigated the specific vulnerability of the gamma-aminobutyric acid (GABA) cortical subset of interneurons, characterized by their calcium-binding protein content, to neuronal death. Dogs representing a large variety of breeds were classified into three groups: young control, aged control, and ccSDAT. In all dogs, the general distribution and cell typology of parvalbumin-, calretinin-, and calbindin-positive neurons were found to be similar to those in the human. As in Alzheimer's disease patients, neurons displaying parvalbumin or calretinin immunoreactivity were resistant and the calbindin-positive ones depleted. Together with aging, amyloid deposition in its early phase (stage II) participates in this specific neuronal death, but with a lower potency. In conclusion, our data provide evidence that preservation of GABAergic cortical interneurons has to be focused on the early stage of beta-amyloid deposition. We also demonstrate the usefulness of dogs of all breeds for investigating the early phases of human brain aging and Alzheimer's disease.
Pugliese
M
M
Unitat de Bioquímica, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
Carrasco
J L
JL
Geloso
M C
MC
Mascort
J
J
Michetti
F
F
Mahy
N
N
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D004285:Dogs; D005260:Female; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D013045:Species Specificity; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D005680:gamma-Aminobutyric Acid