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

Fontana, Bárbara D.; Double, Molly; Mezabrovschi, Roxana; Parcell, Leah; Redhead, Edward S.; Parker, Matthew O.

doi:10.1016/j.neurobiolaging.2021.02.005

Cited by 13 publications

(14 citation statements)

References 95 publications

(131 reference statements)

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“…However, animals tested 3 and 7 days after the exposure had a significant recovery, showing expected baseline parameters for working memory, cognitive flexibility, and abnormal repetitive behavior. In addition, we found that although aging fish showed a decline in the average alternations and alternations across time compared to adult animals (replicating what we have previously reported; Cleal et al, 2021a ), we saw no decline in performance following MS222 exposure, independently of the day after exposure, indicating differential effects of the drug on memory and cognition depending on age. The data here shows, for the first time, the short- and long-term effects on memory and cognition of the use of the anesthetic MS222 in zebrafish and will be useful when planning experimental designs using this species in the future.…”

Section: Discussionsupporting

confidence: 90%

“…Animals were then moved to a recovery tank until equilibrium was regained and normal body movements (preanesthetic appearance) were obtained before being transferred to their home tanks. After recovery, their cognitive and memory-related effects were assessed using the FMP Y -maze protocol (Cleal and Parker, 2018 ; Fontana et al, 2019 ; Cleal et al, 2021a , b ) by evaluating their behavioral profile 1, 2, 3, or 7 days after handling/MS222 exposure.…”

Section: Methodsmentioning

confidence: 99%

“…The FMP Y -maze is a well-characterized task to assess working memory and cognitive flexibility in zebrafish and other translational species (Cleal and Parker, 2018 ; Fontana et al, 2019 ; Cleal et al, 2021a , b ). This task has been validated as a measure of working memory, with several memory-related drugs (scopolamine, MK-801, and SCH-23390), significantly affecting fishes predominant searching strategy, sequential alternations (Cleal et al, 2021b ).…”

Section: Methodsmentioning

confidence: 99%

“…One hundred and seventy zebrafish were used to assess how MS222 affects cognition in adults vs. aging animals. The required sample size was calculated a priori [effect size (d) = 0.25, power = 0.99, alpha = 0.05] based on several published articles using zebrafish in the FMP Y -maze task and extensive experience with this protocol in our laboratory (Cleal and Parker, 2018 ; Fontana et al, 2019 ; Cleal et al, 2021a , b ; Fontana et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, zebrafish have also shown great promise as a model to study the cognitive effects of aging (Yu et al, 2006 ). For example, aged zebrafish have impaired working memory and lower cognitive flexibility compared to adult animals (Cleal et al, 2021a ). Typically, zebrafish changes in cognition associated with aging are evident from around 2 years old, with a gradual cognitive decline observed until 3 years old (estimated life span; Tsai et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

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Tricaine Methanesulfonate (MS222) Has Short-Term Effects on Young Adult Zebrafish (Danio rerio) Working Memory and Cognitive Flexibility, but Not on Aging Fish

Fontana

Alnassar

Parker

2021

Front. Behav. Neurosci.

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Exposure to anesthetic drugs is common in biomedical sciences being part of routine procedures in different translational species, however its impacts on memory and cognition are still debated, having different impacts depending on drug and age. The zebrafish (Danio rerio) is a translational species widely used in behavioral neuroscience, where tricaine methanesulfonate (MS222) is the most acceptable and used drug when conducting routine procedures. Based on this, we investigated the effects of MS222 (100 mg/l) in young adults and aging zebrafish 1, 2, 3, and 7 days after exposure. Animals’ were submitted to the anesthetic procedure until loss of body posture, slowing of opercular movements and lack of response to tail touch with a plastic pipette were achieved, then further left in the drug for 3 min. After that, animals (6 mpf vs. 24 mpf) were transferred to a recovery tank until fully recovered and transferred back to their housing system until further testing in the free movement pattern (FMP) Y-maze, which assesses zebrafish working memory and cognitive lexibility. Young animals had significant impairment in their working memory and cognitive flexibility 1 and 2 days after the exposure to MS222, being fully recovered by day 3 and with no effects 7 days post drug exposure. Increased repetitions were also observed for animals exposed to MS222 which could indicate increased stress-related response in animals up to 2 days after drug exposure. No drug effect was observed in aging animals besides their natural decreased alternations and working memory. Overall, behavioral experiments after routine procedures using MS222 should be performed with caution and need to be delayed, at least 3 days after exposure where working memory, cognitive flexibility, and repetitive behavior are back to normal.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tricaine Methanesulfonate (MS222) Has Short-Term Effects on Young Adult Zebrafish (Danio rerio) Working Memory and Cognitive Flexibility, but Not on Aging Fish

Fontana

Alnassar

Parker

2021

Front. Behav. Neurosci.

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Exposure to Polystyrene Nanoplastics Led to Learning and Memory Deficits in Zebrafish by Inducing Oxidative Damage and Aggravating Brain Aging

Zhou,

Tong,

Tian

et al. 2023

Adv Healthcare Materials

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Nanoplastics (NPs) may pass through the blood‐brain barrier, giving rise to serious concerns about their potential toxicity to the brain. In this study, the effects of NPs exposure on learning and memory, the primary cognitive functions of the brain, were assessed in zebrafish with classic T‐maze exploration tasks. Additionally, to reveal potential affecting mechanisms, the impacts of NPs exposure on brain aging, oxidative damage, energy provision, and the cell cycle were evaluated. Our results demonstrated that NP‐exposed zebrafish took significantly longer for their first entry and spent markedly less time in the reward zone in the T‐maze task, indicating the occurrence of learning and memory deficits. Moreover, higher levels of aging markers (β‐galactosidase and lipofuscin) were detected in the brains of NP‐exposed fish. Along with the accumulation of reactive free radicals, NP‐exposed zebrafish suffered significant levels of brain oxidative damage. Furthermore, lower levels of ATP and cyclin‐dependent kinase 2 and higher levels of p53 were observed in the brains of NP‐exposed zebrafish, suggesting that NPs exposure also resulted in a shortage of energy supply and an arrestment of the cell cycle. These findings suggest that NPs exposure may pose a severe threat to brain health, which deserves closer attention.This article is protected by copyright. All rights reserved

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Passive exposure to visual motion leads to short-term changes in the optomotor response of aging zebrafish

Karaduman,

Karoglu-Eravsar,

Adams

et al. 2024

Behavioural Brain Research

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

Cited by 13 publications

References 95 publications

Tricaine Methanesulfonate (MS222) Has Short-Term Effects on Young Adult Zebrafish (Danio rerio) Working Memory and Cognitive Flexibility, but Not on Aging Fish

Tricaine Methanesulfonate (MS222) Has Short-Term Effects on Young Adult Zebrafish (Danio rerio) Working Memory and Cognitive Flexibility, but Not on Aging Fish

Exposure to Polystyrene Nanoplastics Led to Learning and Memory Deficits in Zebrafish by Inducing Oxidative Damage and Aggravating Brain Aging

Passive exposure to visual motion leads to short-term changes in the optomotor response of aging zebrafish

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