Dopaminergic Modulation of Working Memory and Cognitive Flexibility in a Zebrafish Model of Aging-Related Cognitive Decline
Madeleine Cleal,Barbara D. Fontana,Molly Double,Roxana Mezabrovschi,Leah Parcell,Edward S. Redhead,Matthew O. Parker +6 more
TL;DR: The relationship between cognitive performance and dopamine function of young and aging zebrafish (Danio rerio) was examined in this paper, which revealed age-related decreases in working memory and cognitive flexibility in the Free-Movement Pattern (FMP) Y-maze.
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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 μM) 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
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