Canine Cognitive Dysfunction: study of new therapeutical and diagnostic approaches for the pathology and contributions to research directed to Alzheimer's Disease.
anticholinesterases; biomarkers; cognitive dysfunction.
Canine Cognitive Dysfunction (CCD) is a neurodegenerative disorder that affects older dogs and is very similar to Alzheimer's Disease (AD) in humans. Both pathologies are considered multifactorial and present evidence of b-amyloid deposition; oxidative stress; hyperphosphorylation of Tau protein; imbalance in neurotransmitter levels, such as acetylcholine (ACh); among other factors. Since ACh plays a key role in cognitive processes and many AD treatments are based on the use of acetylcholinesterase inhibitors (AChE), this work aimed to evaluate the efficacy of teas, phytochemicals and synthetic compounds in the in vitro inhibition of this enzyme in dogs brain. This first part of the paper composes chapter 1 of this thesis. The tea of Peumus boldus presented prominence in this study proving effective in the inhibition of this enzyme and with significant antioxidant potential. The phytochemical quercetin and synthetic compounds Cum3 and Cum4 have stood out as competitive inhibitors of AChE activity. The effect of these compounds, as well as of boldo tea, on the serum activity of butyrylcholinesterase (BChE) in dogs was also evaluated. However, all treatments were more effective in inhibiting brain AChE activity than BChE activity in serum. In order to evaluate the effect of CCD on blood enzymes in dogs, blood samples from 48 dogs divided into 5 groups were evaluated: control, risk group, mild DCC, moderate DCC, severe DCC. This part of the paper composes chapter 2 of this thesis. The enzymes evaluated were cholinesterases (using as substrate acetylthiocholine or butyrylthiocholine) and two enzymes of the antioxidant system: catalase and glutathione S-transferase. Although there was no significant difference between the activities of these enzymes in the five groups studied, it was possible to observe changes in the average activities of cholinesterases (using acetylthiocholine as substrate), catalase and GST. These differences show that although such enzymes are not shown to be suitable as CCD biomarkers, they may in future be used as adjuvants in the analysis of disease evolution and in the assessment of response to treatment used. The results obtained in this study, although still early, are promising and may contribute to an advance in the studies of new forms of diagnosis and treatment of CCD.