PUBLICATION
Dopaminergic modulation of working memory and cognitive flexibility in a zebrafish model of aging-related cognitive decline
- Authors
- Cleal, M., Fontana, B.D., Double, M., Mezabrovschi, R., Parcell, L., Redhead, E., Parker, M.O.
- ID
- ZDB-PUB-210307-36
- Date
- 2021
- Source
- Neurobiology of aging 102: 1-16 (Journal)
- Registered Authors
- Keywords
- Aging-related cognitive decline, Dopamine, FMP Y-maze, Memory, Zebrafish
- MeSH Terms
-
- 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology*
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging/psychology*
- Animals
- Cognition/drug effects*
- Cognition/physiology
- Cognitive Dysfunction/etiology*
- Cognitive Dysfunction/psychology*
- Disease Models, Animal*
- Dopamine/physiology*
- Dopamine Agonists/pharmacology*
- Dopamine Plasma Membrane Transport Proteins/genetics
- Dopamine Plasma Membrane Transport Proteins/metabolism
- Down-Regulation/drug effects
- Exploratory Behavior/drug effects
- Gene Expression/drug effects
- Humans
- Memory, Short-Term/drug effects*
- Memory, Short-Term/physiology
- Receptors, Dopamine D1
- Young Adult
- Zebrafish*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 33676049 Full text @ Neurobiol. Aging
Citation
Cleal, M., Fontana, B.D., Double, M., Mezabrovschi, R., Parcell, L., Redhead, E., Parker, M.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.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping