Oxidation and Cognitive Impairment in the Aging Zebrafish

Ruhl, Tim; Jonas, Annika; Seidel, Nathan Ian; Prinz, Nicole; Albayram, Önder; Bilkei-Gorzó, András; Emde, Gerhard von der

doi:10.1159/000433534

Cited by 48 publications

(32 citation statements)

References 50 publications

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“…Mitochondrial dysfunction was found to be associated with social deficits in young individuals [62, 66, 67] and cognitive impairment in aging people and animals [68, 69]. Clinical and animal studies suggest a common neurobiological basis and interrelationship for aggression, diminished cognitive abilities, behavioural disinhibition, and metabolic abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice

et al. 2017

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Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2% of cholesterol and 21% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.

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Section: Discussionmentioning

confidence: 99%

Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice

et al. 2017

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“…The vertebrate brain is especially enriched in long-chain polyunsaturated lipids, such as docosahexaenoic acid (DHA; 22:6 n -3) [4]; therefore, lipid peroxidation is a likely contributor to neuropathology [5]. Zebrafish are a recognized model for studying the pathogenesis of cognitive deficits [6] and the mechanisms underlying behavioral impairments, including the consequences of increased oxidative stressors within the brain [7]. …”

Section: Introductionmentioning

confidence: 99%

Chronic vitamin E deficiency impairs cognitive function in adult zebrafish via dysregulation of brain lipids and energy metabolism

McDougall

Choi

Magnusson

et al. 2017

Free Radical Biology and Medicine

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Zebrafish (Danio rerio) are a recognized model for studying the pathogenesis of cognitive deficits and the mechanisms underlying behavioral impairments, including the consequences of increased oxidative stress within the brain. The lipophilic antioxidant vitamin E (α-tocopherol; VitE) has an established role in neurological health and cognitive function, but the biological rationale for this action remains unknown. In the present study, we investigated behavioral perturbations due to chronic VitE deficiency in adult zebrafish fed from 45 days to 18-months of age diets that were either VitE-deficient (E−) or sufficient (E+). We hypothesized that E− zebrafish would display cognitive impairments associated with elevated lipid peroxidation and metabolic disruptions in the brain. Quantified VitE levels at 18-months in E− brains (5.7 ± 0.1 nmol/g tissue) were ~22-times lower than in E+ (122.8 ± 1.1; n= 10/group). Using assays of both associative (avoidance conditioning) and non-associative (habituation) learning, we found E− vs E+ fish were learning impaired. These functional deficits occurred concomitantly with the following observations in adult E− brains: decreased concentrations of and increased peroxidation of polyunsaturated fatty acids (especially docosahexaenoic acid, DHA), altered brain phospholipid and lysophospholipid composition, as well as perturbed energy (glucose/ketone), phosphatidylcholine and choline/methyl-donor metabolism. Collectively, these data suggest that chronic VitE deficiency leads to neurological dysfunction through multiple mechanisms that become dysregulated secondary to VitE deficiency. Apparently, the E− animals alter their metabolism to compensate for the VitE deficiency, but these compensatory mechanisms are insufficient to maintain cognitive function.

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“…Epigenetic Decrease in global DNA methylation Disruption of gene expression and cellular differentiation [59] Gene expression Decrease in expression of IGF signalingrelated genes Increase in lifespan [16] Increase in smurf2 expression Replicative senescence [16] Increase in hsp1 expression Impaired proteostasis [11] Decrease in tert gene expression Telomere shortening [66] Proteastasis Decrease in Hsp70 levels Impaired cellular stress response and proteostasis [11] Increase in SOD2 activity [64] Increased levels of lipofuscin [65] Genomic DNA fragmentation Senescence and/or cell loss [60] Elevated apoptosis [60] Telomere attrition Significant increase in the loss of telomere repeats…”

Section: Types Of Changes Observations Phenotypes Referencesmentioning

confidence: 99%

“…Dysregulation in lysosomal degradation may be a contributing factor to age-related cognitive dysfunction. For example, increased levels of lipofuscin, a non-degradable end product of lysosomal digestion, and oxidized proteins have been observed in lateral and medial pallial areas of the zebrafish brain at the age of 2 years as compared to 12 month-old animals [65]. Cognitive abilities related to memory are impaired in these fish starting from the age of 18 months, which is after the levels of these cellular byproducts started to increase.…”

Section: Impaired Proteostasismentioning

confidence: 99%

Zebrafish Aging Models and Possible Interventions

Celebi-Birand¹,

Erbaba²,

Ozdemir³

et al. 2018

Recent Advances in Zebrafish Researches

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Across the world, the aging population is expanding due to an increasing average life expectancy. The percentage of elderly over the age of 65 is expected to be more than 15% of the total world population by 2025. As the lifespan increases, there will be a need for maintaining a healthy state for these individuals. Our current knowledge on types and durations of potential anti-aging therapies is quite limited. Recently the zebrafish has emerged as a promising model for understanding the cognitive and neurobiological changes during aging, as well as its use with potential anti-aging interventions. Like humans this model organism ages gradually, displays similar behavioral properties and social characteristics, and in addition, there is a wealth of molecular and genetic tools to uncover the cellular mechanism that contribute to age-related cognitive declines. Drug effect and toxicity can be easily tested in the zebrafish. Therefore, this animal model can provide information about potential therapies that could be translated directly into human populations or provide a more focused treatment direction for testing in other mammalian animal models. The zebrafish will be a powerful tool for uncovering the mysteries of the aging brain.

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Oxidation and Cognitive Impairment in the Aging Zebrafish

Cited by 48 publications

References 50 publications

Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice

Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice

Chronic vitamin E deficiency impairs cognitive function in adult zebrafish via dysregulation of brain lipids and energy metabolism

Zebrafish Aging Models and Possible Interventions

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