Taurine has been shown to play a role in many physiological processes including osmoregulation ( Solis et al., 1988), membrane excitability changes ( Galarreta et al., 1996), and neuronal development where it acts as a putative neurotrophic factor ( Chen et al., 1998 Rak et al., 2014). As a structural analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), taurine mimics GABA action by activating GABA A receptors ( El Idrissi and Trenkner, 2004 Jia et al., 2008), and transport of taurine into neurons occurs via Slc6a6/TauT, the same family of proteins that contribute to GABA transport ( Smith et al., 1992 Uchida et al., 1992 Tomi et al., 2008). Hypotaurine is then converted by hypotaurine dehydrogenase to form taurine ( Vitvitsky et al., 2011). Its biosynthesis is derived from cysteine in which cysteine dioxygenase and cysteinesulfinic acid decarboxylase form hypotaurine. Humans obtain taurine either from the diet or from biochemical synthesis ( Jacobsen and Smith, 1968). Taurine, 2-aminoethanesulfonic acid, is an abundant, free amino acid in human and most animal brains ( Huxtable, 1989) and is also present in the heart, retina, and muscle tissues ( Ripps and Shen, 2012). This study thus provides direct morphological and functional evidence that taurine plays an important role in neurite outgrowth, synaptogenesis, and synaptic transmission during the early stages of brain development and that this role is conserved across both vertebrate and invertebrate species. This effect was comparable, but not additive, to Lymnaea trophic factor-induced synaptogenesis. We found that taurine increased both the incidence of synapse formation (percent of cells that form synapses) and the efficacy of synaptic transmission between the paired neurons. To demonstrate taurine’s direct effects on neurons in the absence of glia and other confounding factors, we next exploited individually identified pre- and postsynaptic neurons from the mollusk Lymnaea stagnalis. We provide direct evidence that when applied at physiological concentrations, taurine exerts a significant neurotrophic effect on neuritic outgrowth and thickness of neurites as well as the expression of synaptic puncta as revealed by immunostaining of presynaptic synaptophysin and postsynaptic PSD95 proteins in rat cortical neurons, indicating direct involvement in synapse development. Here, we investigated whether taurine affects neurite outgrowth, synapse formation, and synaptic transmission between postnatal day 0 rat cortical neurons in vitro, whereas its synaptogenic role was tested more directly using the Lymnaea soma-soma synapse model. Notwithstanding its extensive presence throughout, taurine’s precise role/s during early brain development, function, and repair remains largely unknown in both vertebrate and invertebrate. Like vertebrates, invertebrates maintain high levels of taurine during embryonic and larval development, which decline during aging, indicating a potential developmental role. Taurine deficiency is associated with cardiomyopathy, renal dysfunction, abnormalities of the developing nervous system, and epilepsy which suggests a role specific to excitable tissues. Taurine is a sulfur-containing amino acid that is widely expressed throughout the human brain, heart, retina, and muscle tissues. 3Department of Cell Biology and Anatomy, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada.2Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University, St.1Department of Biology, College of Arts and Sciences, Saint Louis University, St.Brittany Mersman 1,2 Wali Zaidi 3 Naweed I.
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