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

Healthy aging is associated with a decline in memory and executive function, which have both been linked with aberrant dopaminergic signaling. 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 behavioral 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 analyzing exploratory behavior 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.

FMP Y-maze;, aging-related cognitive decline, dopamine;, memory;, zebrafish;

10.1016/j.neurobiolaging.2021.02.005

0197-4580

1-16

Cleal, Madeleine

aadd5f48-ddff-48b9-a6c4-d33b0435bb88

Fontana, Barbara

9374a5d5-c6f0-4cd1-9a8c-34174c6afcd2

Double, Molly

4b2119ac-fb97-4c99-bfcc-34afc7ca1a68

Mezabrovschi, Roxana

c8b4efb6-c6e2-4b3d-b952-1d19cde01214

Parcell, Leah

96615ba9-f081-403c-935f-ea626bb9b2e7

Redhead, Edward

d2342759-2c77-45ef-ac0f-9f70aa5db0df

Parker, Matthew O.

3acfa573-c8d6-400b-91e6-7b04f5275402

June 2021

Cleal, Madeleine

aadd5f48-ddff-48b9-a6c4-d33b0435bb88

Fontana, Barbara

9374a5d5-c6f0-4cd1-9a8c-34174c6afcd2

Double, Molly

4b2119ac-fb97-4c99-bfcc-34afc7ca1a68

Mezabrovschi, Roxana

c8b4efb6-c6e2-4b3d-b952-1d19cde01214

Parcell, Leah

96615ba9-f081-403c-935f-ea626bb9b2e7

Redhead, Edward

d2342759-2c77-45ef-ac0f-9f70aa5db0df

Parker, Matthew O.

3acfa573-c8d6-400b-91e6-7b04f5275402

Cleal, Madeleine, Fontana, Barbara, Double, Molly, Mezabrovschi, Roxana, Parcell, Leah, Redhead, Edward and Parker, Matthew O. (2021) Dopaminergic modulation of working memory and cognitive flexibility in a zebrafish model of aging-related cognitive decline. Neurobiology of Aging, 102, 1-16. (doi:10.1016/j.neurobiolaging.2021.02.005).

Record type: Article

Abstract

Text

Cleal_et_al_(2021) - Accepted Manuscript

Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB)

More information

Accepted/In Press date: 4 February 2021

e-pub ahead of print date: 9 February 2021

Published date: June 2021

Additional Information: Funding Information: MC was funded by a Faculty of Science PhD studentship. BDF was funded by CAPES foundation (Brazil). MOP receives funding from Alzheimer's Research UK, and the Foundation for Liver Research, UK. Publisher Copyright: © 2021

Keywords: FMP Y-maze;, aging-related cognitive decline, dopamine;, memory;, zebrafish;