Canine cognitive dysfunction (CCD) is an age-related neurodegenerative disorder that resembles human Alzheimer’s disease (AD). While oxidative stress has long been implicated in neurodegeneration, Mihevc and colleagues (2020) explored the role of nitrosative stress in the canine brain, a process involving nitric oxide and its reactive derivatives.
Through immunohistochemical analysis of frontal cortex samples from CCD-affected and non-demented control dogs, the researchers detected all three isoforms of nitric oxide synthases (nNOS, eNOS, iNOS) as well as 3-nitrotyrosine (3-NT). Findings showed that nNOS was highly expressed in pyramidal-like neurons in the upper cortical layers of both CCD and control dogs, with significantly elevated levels in CCD-affected brains. Astrocytic nNOS expression was also more prominent in CCD samples.
Additionally, blood vessel wall cells expressed eNOS, while both astrocytes and neurons showed immunoreactivity for this isoform. Crucially, intense 3-NT staining was observed in the cortical regions where amyloid-beta deposits typically spread in late-stage CCD, suggesting overlap with AD pathology. iNOS immunoreactivity was also elevated in these same cortical areas, linking neuroinflammation with nitrosative stress.
These results indicate that nitrosative stress may accelerate neurodegeneration in CCD, ultimately contributing to cognitive decline. By highlighting the interplay between nitric oxide pathways, neuroinflammation, and amyloid pathology, this study provides important mechanistic insights into both canine and human dementia.
Source: Mihevc, S. P., Pipan, M. Z., Štrbenc, M., Rogelj, B., & Majdič, G. (2020). Nitrosative Stress in the Frontal Cortex From Dogs With Canine Cognitive Dysfunction. Frontiers in Veterinary Science, 7, published November 19, 2020.
