Nitrosative Stress in the Frontal Cortex From Dogs With Canine Cognitive Dysfunction.

Sonja Prpar Mihevc,Boris Rogelj,Malan Štrbenc,Maja Zakošek Pipan,Gregor Majdič

doi:10.3389/fvets.2020.573155

Sonja Prpar Mihevc, Boris Rogelj + Show 3 more

Open Access

https://doi.org/10.3389/fvets.2020.573155

Copy DOI

Abstract

Canine cognitive dysfunction (CCD) is an age-related disorder similar to human Alzheimer's disease (AD) that occurs in elderly dogs. Nitrosative stress has been implicated as one of the causes leading to neurodegenerative diseases, particularly AD. Its involvement in the development of CCD has not been studied so far. In the present study, immunohistochemical staining detected all three isoforms of nitric oxide synthases (nNOS, eNOS, and iNOS) and 3-nitrotyrosine (3-NT) in brains from CCD-affected dogs and non-demented control dogs in all layers of the canine frontal cortex. In CCD-affected and non-demented brains, nNOS was highly expressed in pyramidal-like neurons in the upper cortical layers. nNOS has also been observed in astrocytes in the CCD frontal cortex. The nNOS immunohistochemical staining was statistically significantly elevated in dogs with CCD in comparison to non-demented dogs. Blood vessel wall cells were positive for eNOS, which was also expressed in astrocytes and neurons. Intense 3-NT immunoreactivity was observed in the upper cortical layers, where amyloid-beta deposits spread in the last stage of CCD. Brain cells in the same area were highly immunoreactive for iNOS. This infers that neuroinflammation and nitrosative stress might exacerbate the neurodegenerative process in CCD-affected brains, ultimately leading to cognitive impairment.

Highlights

Canine cognitive dysfunction (CCD) is a disease in many aspects similar to human Alzheimer’s disease (AD) [1]
We investigated which cell types expressed the three nitric oxide synthases (NOS) isoforms and 3-NT and whether the expression of nNOS, eNOS, iNOS, and 3-NT is changed in CCD brains
Immunohistochemical staining against Aβ revealed that Aβ plaques are present in the brains of non-demented aged dogs and dogs with CCD

Summary

Introduction

Canine cognitive dysfunction (CCD) is a disease in many aspects similar to human Alzheimer’s disease (AD) [1]. CCD is common in aged dogs, and by 13 years of age, up to 60% of all dogs develop this illness [2]. Dogs show cognitive deficits such as disorientation, memory loss, behavioral changes, and confusion [3]. As in the pathophysiology of AD, the pathological hallmarks leading to the CCD are multifaceted, including the deposition of toxic amyloid-beta (Aβ), brain vascular damage, oxidative brain injury, mitochondrial dysfunction, excitotoxic neuronal damage, neuroinflammation, and cell death [1]. Nitrosative stress has Nitrosative Stress in Canine Brains been implicated as one of the causes leading to the development of neurodegenerative diseases, Alzheimer’s [9]. Its involvement in CCD has not been studied so far

Methods

Results

Conclusion