Dopaminergic modulation of working memory and cognitive flexibility in a zebrafish model of aging-related cognitive decline

Madeleine Elizabeth Cleal, Barbara Dotto Fontana, Molly Double, Mezbrovschi Mezbrovschi, Leah Parcell, Edward S. Redhead, Matt Parker

Research output: Contribution to journalArticlepeer-review

Abstract

Healthy aging is associated with a decline in memory and executive function, which have both been linked with aberrant dopaminergic signalling. We examined the relationship between cognitive performance and dopamine function of young and aging zebrafish (Danio rerio). We revealed age-related decreases in working memory and cognitive flexibility in the Free-Movement Pattern (FMP) Y-maze. An increase in drd5 gene expression in aging adults coincided with a decrease in cognitive performance. Treatment with a D1/D5 receptor agonist (SKF-38393, 35 uM) 30 minutes prior to behavioural assessment resulted in improved working memory in aging zebrafish, but no effect in younger adults. However, an 'overdosing' effect caused by agonist treatment resulted in downregulation of dat expression in 6-month old, treated zebrafish. The translational relevance of these findings was tested in humans by analysing exploratory behaviour in young-adult, 18-35-year olds, and aged adults, 70+ year olds, in a virtual FMP Y-maze. Our findings revealed similar age-related decline in working memory. Thus, strongly supporting zebrafish as a translational model of aging and cognitive decline.
Original languageEnglish
JournalNeurobiology of Aging
Early online date9 Feb 2021
DOIs
Publication statusEarly online - 9 Feb 2021

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