Taurine Supplementation for 48-Months Improved Glucose Tolerance and Changed ATP-Related Enzymes in Avians.

Avians differ from mammals, especially in brain architecture and metabolism. Taurine, an amino acid basic to metabolism and bioenergetics, has been shown to have remarkable effects on metabolic syndrome and ameliorating oxidative stress reactions across species. However, less is known regarding these metabolic relationships in the avian model. The present study serves as a preliminary report that examined how taurine might affect avian metabolism in an aged model system. Two groups of pigeons (Columba livia) of mixed sex, a control group and a group that received 48 months of taurine supplementation (0.05% w/v) in their drinking water, were compared by using blood panels drawn from their basilic vein by a licensed veterinarian. From the blood panel data, taurine treatment generated higher levels of three ATP-related enzymes: glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), and creatine kinase (CK). In this preliminary study, the role that taurine treatment might play in the adult aged pigeon's metabolism on conserved traits such as augmenting insulin production as well as non-conserved traits maintaining high levels of ATP-related enzymes was examined. It was found that taurine treatment influenced the avian glucose metabolism similar to mammals but differentially effected avian ATP-related enzymes in a unique way (i.e., ∼×2 increase in CK and LDH with a nearly ×4 increase in GLDH). Notably, long-term supplementation with taurine had no negative effect on parameters of lipid and protein metabolism nor liver enzymes. The preliminary study suggests that avians may serve as a unique model system for investigating taurine metabolism across aging with long-term health implications (e.g., hyperinsulinemia). However, the suitability of using the model would require researchers to tightly control for age, sex, dietary intake, and exercise conditions as laboratory-housed avian present with very different metabolic panels than free-flight avians, and their metabolic profile may not correlate one-to-one with mammalian data.

Influences of Taurine Pharmacodynamics and Sex on Active Avoidance Learning and Memory.

Researchers have begun to direct their research to focus on the use of taurine as a psychopharmacotherapeutic compound to treat a wide range of health- related conditions as well as neuropathological diseases. Moreover, taurine has been shown to improve emotional and cognitive declines associated with senescence in neurotypical animal models. However, despite these advances in the field of taurine therapeutics, much less is known regarding the effects of sex and taurine on neurotypical animal models that are then manipulated, modified, and/or mutated to study human diseases. The present study sought to investigate this matter in a Long Evans Hooded rat model of mature age (i.e., postnatal day 60-90) in an active avoidance test (AAT). Rats were trained for 20 trials, given a 1 h. test break, retrained for another 20 trials, and then tested at 24 h, 48 h, and 1 week for learning and memory retention. An N = 63 rats were randomly assigned to three groups: (1) Control (n = 22), (2) Taurine Pre-Train (n = 19), and (3) Taurine Post-Train (n = 20). The aim of the present study was to determine the effects of taurine given 15 min before training when compared to being given after training but 15 min before testing at 24 h on learning and memory consolidation of the AAT. The results showed in Control rats that females had shorter latencies to cross in the shuttle box, increased rates of correct learning by the % Avoids/Escapes, and decreased rates of learning errors by the % Shocks. In Taurine Post-Train male rats, taurine treatment decreased their latency to cross in the shuttle box and their rate of learning errors by the % Shocks at 24 h and 48 h Testing, but it had no effect on their rate of correct learning by the % Avoids/Escapes when compared to Control and Taurine Pre-Train male rats. In contrast, Taurine Post-Train female rats increased their latency to cross in the shuttle box during Training, 24 h and 48 h Testing, when compared to the Control and Taurine Pre-Train female rats. Further, Taurine Post-Train female rats decreased their rate of learning % Avoids/Escapes and increased the rate of learning errors % Shocks when compared to Control female rats during Training and 24 h Testing but decreased their rate of learning % Avoids/Escapes and increased the rate of learning errors % Shocks when compared to Taurine Pre-Train female rats across all test conditions. These findings suggest that neurotypical female rats may be more sensitive to the aversive stimuli (i.e., foot shocks) used in the AAT as a motivating factor for learning that may cause paradoxical behavioral learning and memory patterns. This phenomenon raises an important concern for researchers to consider when studying learning and behavioral tests in rodents that use aversive and non-aversive stimuli or a combination of both such as in the AAT. Taurine, albeit neuroprotective, may not have as much benefit in a neurotypical animal model and may increase the susceptibility for anxiogenic behaviors and interfere with cognitive learning and memory behaviors. Therefore, the mechanistic way(s) in which taurine can treat, recovery, ameliorate, and forestall other neuropathological diseases in animal models may have different psychopharmacodynamics and psychopharmacokinetics in a neurotypical animal model and should be studied with caution. This does not preclude the continued investigation of taurine psychopharmacotherapies for neuropathological diseases but encourages the careful investigation of taurine supplementation and treatment in neurotypical animals as paradoxical behavioral and cognitive outcomes have been observed herein.

The effects of chronic taurine supplementation on motor learning.

Taurine is one of the most abundant nonprotein amino acids shown to be essential for the development, survival, and growth of vertebrate neurons. We previously demonstrated that chronic taurine supplementation during neonatal development results in changes in the GABAergic system (El Idrissi, Neurosci Lett 436:19-22, 2008). The brains of mice chronically treated with taurine have decreased levels of GABA(A)ß subunits and increased expression of GAD and GABA, which contributes to hyperexcitability. This down regulation of GABA(A)receptor subunit expression and function may be due to a sustained interaction of taurine with GABA(A)receptors. This desensitization decreases the efficacy of the inhibitory synapses at the postsynaptic membrane. If changes occur in the GABAergic system as a possible compensatory mechanism due to taurine administration, then it is important to study all aspects by which taurine induces hyperexcitability and affects motor behavior. We therefore hypothesized that modification of the GABAergic system in response to taurine supplementation influences motor learning capacity in mice. To test this hypothesis, the rotarod task was employed after chronic taurine supplementation in drinking water (0.05% for 4 weeks). Control animals receiving no taurine supplementation were also tested in order to determine the difference in motor learning ability between groups. Each animal was trained on the rotarod apparatus for 7 days at an intermediate speed of 24 rpm in order to establish baseline performance. On the testing day, each animal was subjected to eight different predefined speeds (5, 8, 15, 20, 24, 31, 33, and 44 rpm). From our observations, the animals that underwent chronic taurine supplementation appeared to have a diminished motor learning capacity in comparison to control animals. The taurine-fed mice displayed minor improvements after repeated training when compared to controls. During the testing session the taurine-fed mice also exhibited a shorter latency to fall, as the task requirements became more demanding.

Changes in gene expression at inhibitory synapses in response to taurine treatment.

We have previously shown that chronic supplementation of taurine to mice significantly ameliorated the age-dependent decline in memory acquisition and retention. We also showed that concomitant with the amelioration in cognitive function, taurine caused significant alterations in the GABAergic and somatonergic system. These changes include increased levels of the neurotransmitters GABA and glutamate, increased expression of both isoforms of GAD and the neuropeptide somatostatin, decreased hippocampal expression of the beta (ß) 2/3 subunits of the GABA(A) receptor, an increase in the number of somatostatin-positive neurons, and an increase in the amplitude and duration of population spikes recorded from CA1 in response to Schaefer collateral stimulation and enhanced paired pulse facilitation in the hippocampus. These specific alterations of the inhibitory system caused by taurine treatment oppose those naturally induced by aging, suggesting a protective role of taurine in this process. In this study, we further investigated the effects of taurine on gene expression of relevant proteins of the inhibitory synapses using qRT-PCR method and found that taurine affects gene expression of various subunits of the GABA(A) receptors and GAD. Increased understanding the effects of taurine on gene expression will increase our understanding of age-related taurine-mediated neurochemical changes in the GABAergic system and will be important in elucidating the underpinnings of the functional changes of aging. Taurine might help forestall the age-related decline in cognitive functions through interaction with the GABAergic system.

Taurine regulation of blood pressure and vasoactivity.

Taurine plays an important role in the modulation of cardiovascular function by acting not only within the brain but also within peripheral tissues. We found that IV injection of taurine to male rats caused hypotension and tachycardia. A single injection of taurine significantly lowered the systolic, diastolic, and mean arterial blood pressure in freely moving Long-Evans control rats. We further confirm the vasoactive properties of taurine using isolated aortic ring preparations. Mechanical responses of circular aortic rings to pharmacological agents were measured by an isometric force transducer and amplifier. We found that bath application of taurine to the aortic rings caused vasodilation which was blocked by picrotoxin. Interestingly, picrotoxin alone induced a constriction of the aortic ring in the absence of exogenously added taurine, suggesting a tonic activation of GABA(A)receptors by circulating either taurine or GABA. Additionally, we found that the endothelial cells express high levels of taurine transporters and GABA(A)receptors. We have previously shown that taurine activates GABA(A)receptors and thus we suggest that the functional implication of GABA(A)receptor activation is the relaxation of the arterial muscularis, vasodilation, and a decrease in blood pressure. Interestingly however, the effects of acute taurine injection were very different than chronic supplementation of taurine. When rats were supplemented taurine (0.05%, 4 weeks) in their drinking water, taurine has significant hypertensive properties. The increase in blood pressure was observed however only in females; males supplemented with taurine did not show an increase in systolic, diastolic, or mean arterial pressure. In both genders however, taurine supplementation caused a significant tachycardia. Thus, we suggest that acute administration of taurine may be beneficial to lowering blood pressure. However, our data indicate that supplementation of taurine to females caused a significant increase in blood pressure. The effect of taurine supplementation on hypertensive rats remains to be seen.