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  • To date glycine receptors have

    2021-10-12

    To date, glycine receptors have been found in five distinct transmembrane protein subunits (one β subunit and four α subunit (α1–α4)), combining to form two different types of functional receptors [4], [14], either α homomeric, the immature extrasynaptic glycine receptor subtype, or αβ heteromeric, the mature form of the receptor that is synaptically located [13], [36]. The physiological and pharmacological properties of glycine receptors depend on the subunit combinations. Picrotoxin, a GABAA receptor antagonist, selectively blocks homomeric glycine receptors but not heteromeric receptors at low concentrations of 50–100μM and is widely used as a tool to distinguish between α-homomeric and αβ-heteromeric glycine receptors [3], [27], [29]. Partial blockade by picrotoxin (50μM) indicates that the PHA neurons express α-homomeric glycine receptors, with the unblocked remainder likely being αβ heteromeric glycine receptors. Glycine in the presence of picrotoxin further confirmed the existence of both homomeric and heteromeric glycine receptor mediated current on PHA neurons. Taurine preferentially activates strychnine-sensitive glycine receptors, whereas higher concentrations (3mM) of taurine activate GABAA receptors [10], [39]. Consistent with the findings in rat hippocampal CA1 neurons [39] and substantia gelatinosa neurons of trigeminal subnucleus caudalis (Vc) [19], the present study showed that taurine at low concentration activates glycine receptors and, at higher concentration (3mM), also activates GABAA receptor mediated current. Further previous studies have also showed that the GABA receptor subunit mRNA and protein are widely expressed in the hypothalamic area of rat [26] and mouse [9] brains. In the literature, taurine is reported as one of the most abundant Cy7 NHS ester after glutamate [11] and might reach concentrations greater than 20mM in neuronal populations and greater than 30mM in glial cells [20], [23]. Further, Palkovits et al., showed that, in rat preoptic hypothalamic area, taurine concentration can reach upto 58.8nmol/mg of protein concentration which has been considered as high taurine concentration [22]. In addition, in mouse supra-optic nucleus the taurine concentration was found to be 67.4nmol/mg [5]. In the hypothalamic SON, taurine released by astrocytes modulates the osmosensitive glycine receptor tone and excitability [5], suggesting a role of taurine release in the hypothalamus. Considering taurine release from the neuronal and glial population [20], [23], in this study, a lower taurine concentration significantly impacted PHA neuron membrane receptors and it can be hypothesized that, taurine may activate α-homomeric/αβ-heteromeric glycine receptors on PHA neurons and GABAA receptors depending on the ambient taurine concentration. In conclusion, in addition to the classical amino acid neurotransmitters such as GABA and glycine, taurine is an important neuro/glio-transmitter that likely plays an important role in preoptic hypothalamic regulation of hormonal release via the hypothalamo-hypophyseal portal system.
    Conflict of interest
    Acknowledgements
    Introduction Antibody-mediated encephalitis is now a well-described entity in adults and children. In children and young adults the commonest antibody-mediated encephalitis is associated with N-methyl-d-aspartate (NMDA) receptor antibodies. The patients present with neuropsychiatric disturbance, seizures, movement disorders (including orofacial dyskinesias), encephalopathy and autonomic disturbance. Phenotypes associated with the antibodies to the VGKC-complexes, and the component proteins (leucine-rich, glioma inactivated 1, LGI1) and CASPR2, include limbic encephalitis (memory loss, seizures, hyponatremia) and the syndrome of facio-brachial dystonic seizures (frequent focal dystonic episodes involving one arm and ipsilateral hemiface, FBDS) both predominantly with VGKC-complex/LGI1 antibodies and, so far, only in older adults. Much rarer is Morvan's syndrome (neuromyotonia, autonomic dysfunction and sleep and circadian rhythm disturbance) with mainly VGKC-complex/CASPR2 antibodies.