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

Dopaminergic modulation of working memory and cognitive flexibility in a zebrafish model of aging-related cognitive decline
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 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.
FMP Y-maze;, aging-related cognitive decline, dopamine;, memory;, zebrafish;
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
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

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.

Text
Cleal_et_al_(2021) - Accepted Manuscript
Restricted to Repository staff only until 9 February 2022.
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More information

Accepted/In Press date: 4 February 2021
e-pub ahead of print date: 9 February 2021
Keywords: FMP Y-maze;, aging-related cognitive decline, dopamine;, memory;, zebrafish;

Identifiers

Local EPrints ID: 446971
URI: http://eprints.soton.ac.uk/id/eprint/446971
ISSN: 0197-4580
PURE UUID: 46fa28a2-7ab9-4eaa-bb43-b5557b37ac2f

Catalogue record

Date deposited: 01 Mar 2021 17:30
Last modified: 25 Nov 2021 18:42

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Contributors

Author: Madeleine Cleal
Author: Barbara Fontana
Author: Molly Double
Author: Roxana Mezabrovschi
Author: Leah Parcell
Author: Edward Redhead
Author: Matthew O. Parker

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