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Part of the natural aging process is a decline in memory and executive function, even in the absence of disease. The dopaminergic system has been implicated in age associated alterations in cognitive flexibility and working memory. Here we examine the relationship between cognitive performance and dopamine function of young-adult and aging zebrafish (Danio rerio). We reveal an age-related decrease in working memory and cognitive flexibility when faced with a negative feedback loop for informing search strategies in the Free-Movement Pattern (FMP) Y-maze. We additionally found a selective role for dopamine D1-like receptor activation, by treatment with partial D1/D5 receptor agonist SKF-38393, for enhancing working memory performance in aged zebrafish, but not for restoring behavioural flexibility. We additionally noted that baseline performance levels were critical to the effect of SKF-38393 on cognitive flexibility. This reduction in behavioural plasticity was accompanied by a down-regulation of the dopamine transporter (dat) and a decrease in metabolic activity. Together, these findings suggest a selective role for cognitive enhancement via dopamine D1 receptors; however, beneficial effects are dependent on behavioural task and baseline performance, emphasising the need for caution when treating cognitive deficits with dopamine agonists to improve cognitive impairment of some tasks. This study further supports the use of zebrafish as a model of aging and cognitive decline.

The importance of oral microbiota has been recently highlighted in human health, such as in Parkinson disease, notably using shotgun metagenomics. One key aspect for efficient shotgun metagenomic analysis relies on optimal microbial sampling and DNA extraction, generally implementing commercial solutions developed to improve sample collection and preservation and provide high DNA quality and quantity for downstream analysis. Because metagenomic studies are today performed on a large number of samples, the next evolution to increase study throughput is with DNA extraction automation. In this study, we proposed a semi-automated DNA extraction protocol for human salivary samples collected with a commercial kit, and compared the outcomes with the DNA extraction recommended by the manufacturer. While similar DNA yields were observed between the protocols, our semi-automated DNA protocol significantly generated higher DNA fragment sizes. Moreover, we showed that the oral microbiome composition was equivalent between DNA extraction methods, even at the species level. This study demonstrates that our semi-automated protocol is suitable for shotgun metagenomic analysis, while allowing for a better sample treatment logistic with reduced technical variability and without compromising the structure of the oral microbiome.

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