Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish

Sarasamma, Sreeja; Audira, Gilbert; Juniardi, Stevhen; Sampurna, Bonifasius Putera; Liang, Sung-Tzu; Hao, Erhong; Lai, Yu‐Heng; Hsiao, Chung-Der

doi:10.3390/ijms19103195

Cited by 58 publications

(54 citation statements)

References 83 publications

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“…A biochemical survey demonstrated that the behavioral alterations may be correlated to oxidative stress, lipid peroxidation, and stress (summarized in Figure 10). it was discovered that the AChE activity in the brain of the zebrafish increased after chronic zinc exposure at 0.1 ppm for 21 days [57]. We suggest that the inconsistency of the AChE activity response toward heavy metals may be correlated to the nature of the animal model and exposure dose and duration (short-term or long-term).…”

Section: Discussionmentioning

confidence: 81%

“…In another study, the AChE levels in Seriola dumerilli were upregulated after Cd exposure at a dose of 50 µg/kg and downregulated at a dose of 100 and 250 µg/kg [56]. In addition, it was discovered that the AChE activity in the brain of the zebrafish increased after chronic zinc exposure at 0.1 ppm for 21 days [57]. We suggest that the inconsistency of the AChE activity response toward heavy metals may be correlated to the nature of the animal model and exposure dose and duration (short-term or long-term).…”

Section: Discussionmentioning

confidence: 97%

“…To assess whether PbCl 2 could impair short-term memory in adult zebrafish, we carried out a passive avoidance test after 4 days (acute treatment), 14 days (sub-chronic treatment) and 30 days (chronic treatment) of exposure (n = 14), referring to previous research with minor modifications [57,62,63]. There were two phases-training and testing-with a 24 h interval between them.…”

Section: Passive Avoidance Test (Short-term Memory Test)mentioning

confidence: 99%

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Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Thi

Audira

et al. 2020

IJMS

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Lead and lead-derived compounds have been extensively utilized in industry, and their chronic toxicity towards aquatic animals has not been thoroughly addressed at a behavioral level. In this study, we assessed the risk of exposure to lead at a waterborne environmental concentration in adult zebrafish by behavioral and biochemical analyses. Nine tests, including three-dimension (3D) locomotion, novel tank exploration, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and a short-term memory test, were performed to assess the behavior of adult zebrafish after the exposure to 50 ppb PbCl 2 for one month. The brain tissues were dissected and subjected to biochemical assays to measure the relative expression of stress biomarkers and neurotransmitters to elucidate the underlying mechanisms for behavioral alterations. The results of the behavioral tests showed that chronic exposure to lead could elevate the stress and anxiety levels characterized by elevated freezing and reduced exploratory behaviors. The chronic exposure to PbCl 2 at a low concentration also induced a sharp reduction of aggressiveness and short-term memory. However, no significant change was found in predator avoidance, social interaction, shoaling, or color preference. The biochemical assays showed elevated cortisol and reduced serotonin and melatonin levels in the brain, thus, altering the behavior of the PbCl 2 -exposed zebrafish. In general, this study determined the potential ecotoxicity of long-term lead exposure in adult zebrafish through multiple behavioral assessments. The significant findings were that even at a low concentration, long-term exposure to lead could impair the memory and cause a decrease in the aggressiveness and exploratory activities of zebrafish, which may reduce their survival fitness.(EC10/NOEC-usually more than 14 days) on fish range from 18 to 1559 µg/L and 44 to 437 µg/L, respectively [3,4].More evidence has shown the detrimental impacts of lead on human health, especially at a neurobehavioral level. The neurotoxicity of chronic exposure to low concentrations of lead can impair cognitive performance in childhood through to adulthood [5][6][7][8][9]. Some studies demonstrated the correlation between the exposure to lead at low concentrations and attention-deficit/hyperactivity disorder (ADHD) in children [10]. The development of the central nervous system can be disrupted when children are exposed to low concentrations of lead for a long period of time (blood lead level below 10 mg/dL) [11]. Therefore, lead toxicity has become a serious issue for human health and environmental protection [6]. According to previous studies, the effect of lead on the nervous system includes the disruption of key molecules during neuronal migration and differentiation, interference with synapse formation mediated by a reduction in neuronal sialic acid production and premature differentiation of glial cells, interference with neurotransmitter release, and disruption of the...

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 97%

Section: Passive Avoidance Test (Short-term Memory Test)mentioning

confidence: 99%

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Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

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Audira

et al. 2020

IJMS

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“…In a previous study, we discovered that low concentrations of ZnCl 2 could reduce the brain acetylcholine content and induce memory loss in zebrafish by using a passive avoidance shuttle box test [25]. However, in the passive avoidance test, there is a tendency that the zebrafish will swim in the dark area as an innate response (usually less than 5 s).…”

Section: Comparison Of Learning Capacity and Memory Retention Betweenmentioning

confidence: 99%

“…The first group without treatment of ZnCl 2 served as control group. The treatment group was waterborne exposed to 100 ppb ZnCl 2 solution for 96 h according to our previous tested condition [25]. After ZnCl 2 incubation, fish were washed three times with excess water and then transferred into individual tanks for memory testing by using a T-maze.…”

Section: Zncl 2 Exposure Incubationmentioning

confidence: 99%

Development of a Modified Three-Day T-maze Protocol for Evaluating Learning and Memory Capacity of Adult Zebrafish

Hieu

Ánh

Audira

et al. 2020

IJMS

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A T-maze test is an experimental approach that is used in congenital research. However, the food reward-based protocol for the T-maze test in fish has low efficiency and a long training period. The aim of this study is to facilitate the T-maze conditions by using a combination of the principles of passive avoidance and a spatial memory test. In our modified T-maze settings, electric shock punishment (1–2 V, 0.3–0.5 mA) is given at the left arm, with a green cue at the right arm. Also, the depth of both arms of the T-maze was increased. The parameters measured in our T-maze design were latency, freezing time, and time spent in different areas of the T-maze. We validated the utility of our modified T-maze protocol by showing the consistent finding of memory impairment in ZnCl2−treated fish, which has been previously detected with the passive avoidance test. In addition, we also tested the spatial memory performance of leptin a (lepa) mutants which displayed an obesity phenotype. The results showed that although the learning and memory performance for lepa KO fish were similar to control fish, they displayed a higher freezing behavior during the training phase. In conclusion, we have established a modified T-maze protocol that can be used to evaluate the anxiety, learning, and memory capacity of adult zebrafish within three days, for the first time.

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Duloxetine ameliorates valproicacid‐inducedhyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish

et al. 2021

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Syndromic autism spectrum disorders (ASDs) are characterized by impaired social communication and repetitive/stereotyped behaviors. Currently available therapeutic agents against ASD have limited efficacy. Thus, searching for novel and effective drugs ameliorating core symptoms, in particular social deficits, is of utmost importance. Duloxetine (DLX), an antidepressant that has been identified as an agonist mimetic for the cell adhesion molecule L1, exhibits beneficial functions in vitro and in vivo. Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)‐triggered hyperactivity, anxiety‐like behavior and social deficits in zebrafish. Embryonic exposure to VPA reduced survival in a dose‐ and time‐dependent manner, delayed hatching, and also resulted in a significant number of malformed larvae. After initial dose–response experiments in zebrafish larvae, 10 μM VPA exposure between 0.33 and 4.5 days post fertilization (dpf) was identified as an effective concentration that led to an early and persistent ASD‐like phenotype in zebrafish. ASD‐like elevated acetylcholine esterase (AChE) activity and reduced Akt–mTOR signaling was observed in zebrafish whole brain. Acute administration of DLX (4.5–6 dpf) reduced the VPA‐induced ASD‐like phenotype in zebrafish larvae. Additionally, such early‐life acute DLX treatment had long‐term effects in ameliorating social impairments, hyperactivity, and anxiety‐like behaviors through adulthood. This was accompanied by reduced AChE activity and by normalized Akt–mTOR signaling. Overall, DLX treatment showed a long‐term therapeutic effect on autistic‐like behaviors, and alteration of AChE activity and Akt–mTOR signaling were identified as crucial in the VPA‐induced ASD zebrafish model.

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Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish

Cited by 58 publications

References 83 publications

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Development of a Modified Three-Day T-maze Protocol for Evaluating Learning and Memory Capacity of Adult Zebrafish

Duloxetine ameliorates valproicacid‐inducedhyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish

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