Taurine counteracts the neurotoxic effects of streptozotocin-induced diabetes in rats.

Diabetes is a chronic metabolic disease associated with oxidative stress, damage to biomolecules such as DNA, and neuroinflammation. Taurine, a sulfur-containing amino acid widespread in the brain, has neuroprotective properties that might prevent tissue injury and DNA damage induced by chronic hyperglycemia. We evaluated the effects of chronic taurine treatment on oxidative stress parameters, DNA damage and inflammatory markers in the frontal cortex, and hippocampus of streptozotocin-induced diabetic rats. Diabetic rats displayed increased levels of reactive oxygen species (ROS) and DNA damage in both areas, evidencing the pro-oxidant effects of diabetes in the brain. Moreover, this condition increased levels of several inflammatory mediators, such as IL-6, IL-12, TNF-γ, and IFN-α, more pronouncedly in the hippocampus. Supporting our hypothesis, taurine treatment reduced ROS, DNA damage, and inflammatory cytokine levels, providing evidence of its beneficial effects against genotoxicity and neuroinflammation associated with diabetes. Our data endorse the necessary clinical trials to evaluate the efficacy and safety of taurine supplementation in the prevention and treatment of neurochemical and metabolic alterations related to diabetes.

Low-cost apparatus for cigarette smoke exposure in rats.

BACKGROUND: The effects of tobacco smoke on the central nervous system are usually studied with isolated nicotine, ignoring other compounds present in cigarette smoke. The few studies that use in vivo whole-body cigarette smoke exposure are usually performed in expensive commercial apparatus. NEW METHOD: We presented a feasible, safe, and low-cost apparatus for cigarette smoke exposure in rodents. RESULTS: Rats exposed to cigarette smoke in this apparatus showed cotinine levels similar to human active smokers. Additional results showed that cigarette smoke exposure increased glutamate and aspartic acid levels and decreased leucine, isoleucine, ornithine, phenylalanine, and tryptophan levels in the cerebrospinal fluid of rats. COMPARISON WITH EXISTING METHOD(S): Our apparatus is feasible, safe, and costs 67-fold less than a commercial automatized smoking machine. Beyond the low cost, it does not require specialized knowledge for building or maintenance. CONCLUSIONS: We concluded that our low-cost apparatus is reliable and reproduces cigarette smoke use in humans.

Taurine enhances voluntary alcohol intake and promotes anxiolytic-like behaviors in rats.

Taurine is an amino acid usually added to energy drinks. In rodents, acute taurine administration decreases voluntary alcohol intake, and subchronic administration restores different behavioral features impaired by alcohol withdrawal. In the present study, we evaluated the effects of chronic taurine treatment on voluntary alcohol consumption and changes in behavioral parameters in rats. Adult male Wistar rats were divided into two groups and were allowed to choose from two bottles containing 20% alcohol or 0.08% saccharin (vehicle solution), or two bottles containing vehicle, 24 h per day, for 5 weeks. After 3 weeks, rats received 100 mg/kg taurine (TAU) or saline (SAL) intraperitoneally once a day for 2 weeks, and daily alcohol consumption was monitored. On days 22 and 33, rats were tested in the open-field, and on day 34, they were exposed to the light/dark task (LDT). Our results show for the first time that chronic taurine treatment enhanced voluntary alcohol intake and preference in rats, and that these changes were accompanied by an anxiolytic-like phenotype in alcohol-treated rats, possibly due to its synergistic effect with alcohol on the dopaminergic and GABAergic systems.

Correlations between subunits of GABAA and NMDA receptors after chronic alcohol treatment or withdrawal, and the effect of taurine in the hippocampus of rats.

Chronic use of alcohol and its withdrawal impairs the delicate balance between GABAergic and glutamatergic systems. This imbalance includes changes in GABA receptors - importantly in GABAA subtypes - and glutamate receptors, especially in NMDA subtypes. A better comprehension of the different roles of GABAAR and NMDAR subunits could be helpful to define new strategies to counteract the deleterious effects observed during alcohol withdrawal. Taurine, a sulfonated amino acid, has been proposed to attenuate alcohol withdrawal symptoms due to its neuromodulatory properties. In this study, we evaluated the correlations between GABAAR and NMDAR subunits in the hippocampus of rats chronically treated with alcohol or in alcohol withdrawal, and the effects of taurine treatment on these parameters. Male Wistar rats received alcohol (2 g/kg) or water by oral gavage (control), 2 × /day, for 28 days. From day 29 to day 33, withdrawal rats received water instead of alcohol and all groups were reallocated to receive 100 mg/kg taurine or saline intraperitoneally (i.p.), once a day. On day 34, rats were euthanized and the hippocampus was dissected for GABAAR α1, α4, δ, and γ2 and NMDAR GluN2A and GluN2B subunits mRNA expression determination by RT qPCR. There were no differences between groups in the studied GABAAR and NMDA subunits. However, we observed a correlation of α1 and γ2 subunits induced by taurine, while in the alcohol group there was a correlation between α4 and GluN2A. In the group treated with alcohol and taurine, we observed an extra correlation, between α1 and GluN2A. After 5 days of withdrawal, a correlation observed in the control group, between δ and GluN2A, was reestablished. The correlation found between subunits suggests a neuroadaptation of GABAergic and glutamatergic systems in withdrawal rats. Results from this study contribute to the elucidation of the mechanisms beyond neuroadaptations observed in alcohol use and withdrawal.

Combined use of alcohol and cigarette increases locomotion and glutamate levels in the cerebrospinal fluid without changes on GABAA or NMDA receptor subunit mRNA expression in the hippocampus of rats.

Interactions on neurotransmitter systems in the reward pathways may explain the high frequency of combined use of alcohol and cigarettes in humans. In this study, we evaluated some behavioral and neurochemical changes promoted by chronic exposure to alcohol and cigarette smoke in rats. Adult rats were administered with 2 g/kg alcohol (v.o.) or/and inhaled the smoke from 6 cigarettes, twice/day, for 30 days. Behavioral tests were performed 3 h after the alcohol administration and 1 h after the last exposure to cigarette smoke in the morning. Cerebrospinal fluid was collected for glutamate determination and the hippocampus was dissected for GABAA and NMDA receptor subunits mRNA expression determination. Results showed that the combined use of alcohol and cigarette smoke (ALTB) in rats increased the locomotor activity and all interventions decreased anxiety-like behaviors. Despite being on a short-term withdrawal, the cigarette smoke exposure decreased the percentage of open arm entries in the elevated plus maze test, which was prevented by combined use with alcohol. Even though GABAA and glutamate receptor subunits expression did not change in the hippocampus, glutamate levels were significantly higher in the cerebrospinal fluid from ALTB rats. Therefore, we showed that the combined use of alcohol and cigarette maintained a psychostimulant effect after a short-term withdrawal that was associated with the elevated glutamatergic activity. The combined use also prevented anxiety-like signs in cigarette smoke exposure rats, decreasing an adverse effect caused by nicotine withdrawal. These results could explain, in part, the elevated frequency of combined use of these two drugs of abuse in humans.

Acute intraperitoneal administration of taurine decreases the glycemia and reduces food intake in type 1 diabetic rats.

Taurine, an amino acid with antioxidant and osmoregulatory properties, has been studied for its possible antidiabetic properties in type 1 and type 2 diabetic animals. In type 2 diabetic mice, taurine decreases blood glucose through increased insulin secretion and insulin receptor sensitization. However, insulin is absent in type 1 diabetic individuals. The aim of this study was to evaluate the effects of taurine on parameters related to the energy balance that could explain the metabolic action of this amino acid in type 1 diabetic rats. Control and streptozotocin-induced diabetic rats received saline or taurine (100 mg/kg/day), intraperitoneally, for 30 days. Parameters such as palatable food intake, gastrointestinal transit rate, serum glucose, insulin, leptin, and glucagon levels were measured 60 min after the last taurine administration. Liver, kidneys, heart, and retroperitoneal fat were dissected and weighted. Glycogen levels were measured in the liver and soleus muscle. Our results showed that acute taurine administration decreased glycemia. It also decreased food intake in diabetic rats, without affecting other metabolic parameters. Altogether, our results suggest that in type 1 diabetic rats, taurine decreases blood glucose by a non-insulin-dependent mechanism. Due to the safety profile of taurine, and its effect on glycemia, this amino acid may help to design new drugs to add benefit to insulin therapy in type 1 diabetic individuals.

Taurine restores the exploratory behavior following alcohol withdrawal and decreases BDNF mRNA expression in the frontal cortex of chronic alcohol-treated rats.

Alcohol use disorder is an alarming health problem, and the withdrawal symptoms increase the risk of relapse. We have hypothesized that taurine, a multitarget substance acting as a gamma-aminobutyric acid A receptor (GABAAR) positive modulator and a partial inhibitor of N-methyl-d-aspartate (NMDA) glutamate receptors, may reduce the withdrawal symptoms or modify behaviors when combined with alcohol. Therefore, we investigated the effects of taurine on behavior in the open field test (OFT), the GABAAR α2 subunit and BDNF mRNA expression in the frontal cortex of rats after chronic alcohol treatment or upon withdrawal. Rats received alcohol 2g/kg (alcohol and withdrawal groups) or water (control group) twice daily by oral gavage for 28days. On day 29, the withdrawal rats received water instead of alcohol, and all groups were reallocated to receive 100mg/kg taurine or vehicle intraperitoneally, once a day for 5days. On day 33, the rats were exposed to OFT; 18h later, they were euthanized, and the frontal cortex was dissected for GABAAR α2 subunit detection and BDNF mRNA expression determination by real-time quantitative PCR. Taurine administration restored rearing behavior to the control levels in the withdrawal rats. Taurine also showed anxiolytic-like effects in control rats and did not change the behaviors in the chronic alcohol group. Chronic alcohol treatment or withdrawal did not change the GABAAR α2 subunit or BDNF mRNA expression in the frontal cortex, but taurine decreased the α2 subunit level in control rats and to the BDNF levels in the alcohol rat group. We conclude that taurine restored exploratory behavior after alcohol withdrawal but that this effect was not related to the GABAAR α2 subunit or BDNF mRNA expression in the frontal cortex of the rats.