Cotreatment of Small Gold Nanoparticles Protects Against the Increase in Cerebral Acetylcholinesterase Activity and Oxidative Stress Induced by Acute Ethanol Exposure in the Zebrafish.

Gold nanoparticles (GNP) have emerged as an alternative to biomaterials in biomedical applications. Research has clearly demonstrated the relative safety and low toxicity of these molecules. However, the possible neuroprotective effect of GNP on the central nervous system (CNS) and its relationship with neurological and psychiatric disorders remain unclear. Zebrafish is a reliable model to investigate the impact of ethanol (EtOH) consumption on the CNS, including reward signaling such as the cholinergic neurotransmission system. Here, we investigated whether cotreatment or pretreatment with GNP prevented EtOH-induced changes in acetylcholinesterase activity and oxidative stress in the brain of zebrafish. We exposed adult zebrafish to 2.5 mg·L-1 GNP 1 h prior to EtOH (1% v/v) treatment for 1 h, and cotreated adult zebrafish simultaneously with both substances for 1 h. Pretreatment with GNP did not prevent EtOH-induced increase in the acetylcholinesterase activity, whereas cotreatment with 2.5 mg·L-1 GNP and EtOH protected against this increase. The results also suggested similar protective effect on oxidative stress parameters in the zebrafish pretreated with GNP at 2.5 mg·L-1. GNP significantly decreased the levels of thiobarbituric acid reactive species and dihydrodichlorofluorescein levels when cotreated with EtOH. GNP also prevented EtOH-induced increase in superoxide dismutase and catalase activities, suggesting a modulatory role of GNP in enzymatic antioxidant defenses. Our results showed that GNP was able to modulate the disruption of cholinergic and oxidative homeostasis in the brain of zebrafish. These findings indicate for the first time that zebrafish is an interesting perspective to investigate nanoparticles against disorders related to alcohol abuse.

Cholinergic system and exploratory behavior are changed after weekly-binge ethanol exposure in zebrafish.

Binge drinking is characterized by excessive alcohol consumption in a short period of time and is associated with a poor quality of life. Zebrafish are commonly used to investigate neurochemical, behavioral, and genetic parameters associated with ethanol (EtOH) exposure. However, few studies have used zebrafish as a model to investigate binge EtOH exposure. In order to elucidate the potential neurobehavioral impairments evoked by binge EtOH exposure in zebrafish, animals were immersed in 1.4% EtOH for 30 min three consecutive times with intervals of one week. Neurobehavioral parameters were analyzed immediately following the third exposure, as well as 2 and 9 days later. Brain choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were reduced 9 days after the treatment. Thiobarbituric acid-reactive species and dichlorodihydrofluorescein levels were increased immediately after the treatment, but both returned to normal levels 2 days after the treatment. Catalase and glutathione reductase were impaired 2 and 9 days after the treatment. No alteration was observed in superoxide dismutase and glutathione peroxidase activities. EtOH treatment did not alter brain expression of inflammatory genes such as il-1ß, il-10, and tnf-α. Zebrafish displayed anxiolytic-like behavior immediately after the last exposure, though there was no behavioral alteration observed 9 days after the treatment. Therefore, binge EtOH exposure in zebrafish leads to long lasting brain cholinergic alteration, probably related to oxidative stress immediately after the exposure, which is independent of classical inflammatory markers.

Cholinergic System and Oxidative Stress Changes in the Brain of a Zebrafish Model Chronically Exposed to Ethanol.

Ethanol is a widely used drug, and excess or even moderate consumption of ethanol is associated with changes in several neurotransmitter systems, including the cholinergic system. The incidence of alcoholic dementia and its insults are well supported by multiple studies, although the mechanisms of neurotoxicity are still poorly understood. Considering that zebrafish have a complete central nervous system (CNS) and that several signaling systems have already been identified in zebrafish, this neurotoxicological model has become useful. In the present study, we investigated the long-term effects of ethanol consumption on the cholinergic system, on oxidative stress, and on inflammatory parameters in the zebrafish brain. Animals were exposed to 0.5% (v/v) ethanol for 7, 14, and 28 days. Ethanol inhibited choline acetyltransferase activity after 7 and 14 days but not after 28 days. Acetylcholinesterase activity did not change after any of the exposure periods. When compared to the control group, thiobarbituric acid reactive species and dichlorodihydrofluorescein levels were increased after chronic ethanol exposure. Antioxidant activity promoted by the CAT/SOD ratio was altered after chronic ethanol exposure, suggesting that EtOH can induce oxidative damage in the zebrafish brain. In contrast, nitrate and nitrite levels and sulfhydryl content were not altered. Ethanol did not modify gene expression of the inflammatory cytokines il-1b, il-10, or tnf-α in the zebrafish brain. Therefore, the cholinergic system and the oxidative balance were targeted by chronic ethanol toxicity. This neurochemical regulatory mechanism may play an important role in understanding the effects of long-term ethanol consumption and tolerance in zebrafish model studies.