Carnosine Mitigates Cognitive Impairment and Dopamine Release in an Okadaic Acid-Induced Zebrafish Model with Alzheimer's Disease-like Symptoms.

Abstract

Alzheimer's disease (AD), the leading cause of dementia, affects 1 in 9 people aged 65 and older. The disease impacts patients on multiple levels, from memory and problem-solving issues to difficulties with basic functions and personality changes. Unfortunately, there is only a handful of FDA-approved drugs, and none of them offer an effective cure. Therefore, recent strategies have focused on preventing and delaying disease onset, rather than curing already developed pathological changes in the brain. In this study, we investigated the therapeutic potential of carnosine (CAR), a naturally occurring dipeptide known for its multimodal mechanism of action, such as the ability to mitigate neuroinflammation, oxidative stress, and deficiencies in neurotropic factors, all of which are connected with aging-related cognitive decline and an increased risk of developing dementia. For this purpose, we utilized an okadaic acid-induced zebrafish model of AD, which replicates some of the key features of the disease, including hyperphosphorylation of tau protein, changes in Aβ-fragments, and cognitive decline. By employing a latent learning behavioral assay and fast-scan cyclic voltammetry, we evaluated the effect of CAR on the prevention of cognitive decline and neurochemical changes in the AD-like zebrafish brain. Our findings revealed that CAR prevents impaired learning and motor dysfunction in a sex-dependent manner and reduces anxiety-like behavior. Additionally, we found that CAR inhibits dopamine release impairment. Hence, our study demonstrates the potential of CAR as a promising candidate for further investigations focused on identifying molecules that could potentially serve as therapeutics for delaying the onset of AD.