Relation between vitamins of the b complex, GABA and glutamate, and their role in neurocognitive disorders -Brief review
Keywords:GABA, Glutamate, Vitamins B, Neuroplasticity, Neurotransmission.
Vitamins, especially the water-soluble complex of vitamins B, are highlighted in the daily clinical practice. Numerous studies emphasize the need for supplementation, mainly in groups with deficiency of these vitamins, such as the elderly, pregnant women, children and patients with diseases associates with cognitive disorder. Thiamine (B1), a vitamin of the diet, is an important cofactor for the three key enzymes involved in the citric acid cycle and the pentose phosphate cycle. Pyridoxine (B6) and cobalamin (B12) act in the CNS as a cofactor in the metabolism reactions of homocysteine. Deficiency of some neurotransmitter precursors can also cause symptoms of attention deficit hyperactivity disorder in children, especially amino acid and vitamin B deficiency. Inhibitory and excitatory neurotransmitters regulate diverse behavioral processes, including sleep, learning, memory and sensation of pain. They are also implicated in many pathological processes, such as epilepsy and neurotoxicity. Studies suggest that the excitatory amino acids may play a role in learning and memory. The binding of glutamate to its receptor triggers molecular and cellular events associated with numerous physiological and pathophysiological pathways, including the development of an increased sensation of pain (hyperalgesia), brain neurotoxicity or synaptic alterations involved in certain types of memory formation. Between the two major classes of neuroactive amino acids, Î³-aminobutyric acid (GABA) is the major inhibitory amino acid. It is known that GABA plays a fundamental role in encoding information and behavioral control, in the regulation of motor function and in motor learning. The inter-relationships between diet, the brain and behavior are complex. However, micronutrients are known to have a direct influence on cognitive function through their involvement in the energy metabolism of neurons and glia cells, the synthesis of neurotransmitters, receptor binding and the maintenance of membrane ion pumps.
 M.N. GarcÃa-Casal, C. Osorio, M. Landaeta, I. Leets, P. Matus, F. Fazzino, E. Marcos. High prevalence of folic acid and vitamin B12 deficiencies in infants, children, adolescents and pregnant women in Venezuela. Eur J Clin Nutr, v. 59, n. 9, p. 1064-70, Sep 2005. ISSN 0954-3007 (Print) 0954-3007.
 R. Obeid; W. Herrmann. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett, v. 580, n. 13, p. 2994-3005, May 29 2006. ISSN 0014-5793 (Print) 0014-5793.
 P. Verhoef, M.J. Stampfer, J.F. Buring, J.M. Gaziano, R.H. Allen, S.P. Stabler, et al. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol, v. 143, n. 9, p. 845-59, May 1 1996. ISSN 0002-9262 (Print) 0002-9262.
 J. Selhub, L.C. Bagley, J. Miller, I.H. Rosenberg. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr, v. 71, n. 2, p. 614s-620s, Feb 2000. ISSN 0002-9165 (Print) 0002-9165.
 M.J. Medrano, M.J. Sierra, M.T. Olalla, G. LÃ³pez-Abente. The association of dietary folate, B6, and B12 with cardiovascular mortality in Spain: an ecological analysis. Am J Public Health, v. 90, n. 10, p. 1636-8, Oct 2000. ISSN 0090-0036 (Print) 0090-0036.
 J.L. Simpson. L.B. Beiley, K. Pietrzik, B. Shane, W. Holzgreve. Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part I--Folate, Vitamin B12, Vitamin B6. J Matern Fetal Neonatal Med, v. 23, n. 12, p. 1323-43, Dec 2010. ISSN 1476-4954.
 L. Bettendorff, F. Mastrogiacomo, S.J. Kish, T. Grisar. Thiamine, Thiamine Phosphates, and Their Metabolizing Enzymes in Human Brain. J Neurochem, 1996. ISSN 1.
 R.H. Haas. Thiamin and the brain. Annu Rev Nutr, v. 8, p. 483-515, 1988. ISSN 0199-9885 (Print) 0199-9885.
 C.G. Harper, M. Giles, R. Finlay-Jones. Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy. J Neurol Neurosurg Psychiatry, v. 49, n. 4, p. 341-5, Apr 1986. ISSN 0022-3050 (Print) 0022-3050.
 S.R. Pitkin; L.M. Savage. Age-related vulnerability to diencephalic amnesia produced by thiamine deficiency: the role of time of insult. Behav Brain Res, v. 148, n. 1-2, p. 93-105, Jan 5 2004. ISSN 0166-4328 (Print) 0166-4328.
 M.H. Donovan, U. Yazdani, R.D. Norris, D. Games, D.C. German, A.J. Eisch. Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease. J Comp Neurol, v. 495, n. 1, p. 70-83, Mar 1 2006. ISSN 0021-9967 (Print) 0021-9967.
 M. Gold, R.A. Hauser, M.F. Chen. Plasma thiamine deficiency associated with Alzheimer's disease but not Parkinson's disease. Metab Brain Dis, v. 13, n. 1, p. 43-53, Mar 1998. ISSN 0885-7490 (Print) 0885-7490.
 T.M. Jeitner, H. Xu, G.E. Gibson. Inhibition of the alpha-ketoglutarate dehydrogenase complex by the myeloperoxidase products, hypochlorous acid and mono-N-chloramine. J Neurochem, v. 92, n. 2, p. 302-10, Jan 2005. ISSN 0022-3042 (Print) 0022-3042.
 N.Y. Calingasan, S.E. Gandy, H. Barker, K.F. Sheu, J.D. Smith, B.T. Lamb, et al. Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency. Am J Pathol, v. 149, n. 3, p. 1063-71, Sep 1996? ISSN 0002-9440 (Print) 0002-9440.
 E. Drapeau, W. Mayo, C. Aurousseau, M.L. Moal, P.V. Piazza, D.N. Abrours. Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. PNAS, v. 100, n. 24, 2003. ISSN 24.
 S.A. Goldman; F. Nottebohm. Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. Proc Natl Acad Sci U S A, v. 80, n. 8, p. 2390-4, Apr 1983. ISSN 0027-8424 (Print)
 H. Van Praag, B.R. Christie, T.J. Sejnowski, F.H. Gage. Running enhances neurogenesis, learning, and long-term potentiation in mice. In: (Ed.). Proc Natl Acad Sci U S A, v.96, 1999. p.13427-31. ISBN 0027-8424 (Print) 1091-6490 (Electronic). https://doi.org/10.1073/pnas.96.23.13427.
 S. Becker. A computational principle for hippocampal learning and neurogenesis. Hippocampus, v. 15, n. 6, p. 722-738, 2005. https://doi.org/10.1002/hipo.20095.
 M. CarlÃ©n, R.M. Cassidy, H. Brismar, G.A. Smith, L.W. Enquist, J. FrisÃ©n. Functional integration of adult-born neurons. Current Biology, v. 12, n. 7, p. 606-608, 2002. https://doi.org/10.1016/S0960-9822(02)00771-6.
 N.B. Hastings; E. Gould. Rapid extension of axons into the CA3 region by adult-generated granule cells. Journal of Comparative Neurology, v. 413, p. 146-154, 1999. https://doi.org/10.1002/(SICI)1096-9861(19991011)413:1<146::AID-CNE10>3.0.CO;2-B.
 E.A. Markakis; F.H. Gage. Adultâ€generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles. Journal of comparative neurology, v. 406, n. 4, p. 449-460, 1999. https://doi.org/10.1002/(SICI)1096-9861(19990419)406:4<449::AID-CNE3>3.0.CO;2-I.
 H.A.Cameron, C.S. Woolley, B.S. McEwen, E. Gould. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience, v. 56, n. 2, p. 337-44, Sep 1993. ISSN 0306-4522 (Print) 0306-4522.
 H.G. Kuhn, H. Dickinson-Anson, F.H. Gage. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci, v. 16, n. 6, p. 2027-33, Mar 15 1996. ISSN 0270-6474 (Print) 0270-6474
 H. Van Praag, A.F. Schinder, B.R. Christie, N. Toni, T.D. Palmer, F.H. Gage. Functional neurogenesis in the adult hippocampus. Nature, v. 415, n. 6875, p. 1030-1034, 2002. https://doi.org/10.1038/4151030a.
 N. Zhao, C. Zhong, Y. Wang, Y. Zhao, N. Gong, G. Zhou, T. Xu, Z. Hong. Impaired hippocampal neurogenesis is involved in cognitive dysfunction induced by thiamine deficiency at early pre-pathological lesion stage. Neurobiology of disease, v. 29, n. 2, p. 176-185, 2008. https://doi.org/10.1016/j.nbd.2007.08.014.
 D. Benton, J. Haller, J. Fordy. Vitamin supplementation for 1 year improves mood. Neuropsychobiology, v. 32, n. 2, p. 98-105, 1995. https://doi.org/10.1159/000119220.
 J. BroÅ¾ek, H. Guetzkow. Psychologic effects of thiamine restriction and deprivation in normal young men. The American journal of clinical nutrition, v. 5, n. 2, p. 109-120, 1957.
 L.J. Smidt, F.M. Cremin, L.E. Grivetti, A.J. Clifford. Influence of thiamin supplementation on the health and general well-being of an elderly Irish population with marginal thiamin deficiency. Journal of gerontology, v. 46, n. 1, p. M16-M22, 1991. https://doi.org/10.1093/geronj/46.1.M16.
 H. Heseker, W. Kiibler, J. Westenhssfer, V. Pudel. Psychische Verfinderungen als Friihzeichen einer suboptimalen Vitaminversorgung. Erniihrungs Umschau 1990, 37:87-94.
 R.F. Harrell. Mental response to added thiamine. Journal of Nutrition, v. 31, n. 3, p. 283-98, 1946.
 R. Clarke, A.D. Smith, K.A. Jobst. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Archives of neurology, v. 55, n. 11, p. 1449-1455, 1998. https://doi.org/10.1001/archneur.55.11.1449.
 R. R. McLean; M.T. Hannan. B vitamins, homocysteine, and bone disease: epidemiology and pathophysiology. Current osteoporosis reports, v. 5, n. 3, p. 112-119, 2007. https://doi.org/10.1007/s11914-007-0026-9.
 D.G. Weir; J.M. Scott. Brain function in the elderly: role of vitamin B12 and folate. Br Med Bull, v. 55, n. 3, p. 669-82, 1999. ISSN 0007-1420 (Print) 0007-1420.
 M.D. Thompson, A. Killoran, M.E. Percy, M. Nezarati, D.E.C. Cole, P.A. Hwang. Hyperphosphatasia with neurologic deficit: a pyridoxine-responsive seizure disorder? Pediatr Neurol, v. 34, n. 4, p. 303-7, Apr 2006. ISSN 0887-8994 (Print) 0887-8994.
 I.I. Kruman, C. Culmsee, S.L. Chan, Y. Kruman, Z. Guo, L.R. Penix, M.P. Mattson. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci, v. 20, n. 18, p. 6920-6, Sep 15 2000. ISSN 0270-6474 (Print) 0270-6474.
 R.J. Reiter, D.X. Tan, M.A. Pappolla. Melatonin relieves the neural oxidative burden that contributes to dementias. Ann N Y Acad Sci, v. 1035, p. 179-96, Dec 2004. ISSN 0077-8923 (Print) 0077-8923.
 D. Fontanari, C.D. Palma, G. Gioretti, F. Violante, M. Voltolina. Effects of S-adenosyl-L-methionine on cognitive and vigilance functions in the elderly. Current Therapeutic Research, v. 55, n. 6, 1994. ISSN 6.
 P.E. Gold. Role of glucose in regulating the brain and cognition. Am J Clin Nutr, v. 61, n. 4 Suppl, p. 987s-995s, Apr 1995. ISSN 0002-9165 (Print) 0002-9165.
 L. Cahill; M.T. Alkire. Epinephrine enhancement of human memory consolidation: interaction with arousal at encoding. Neurobiol Learn Mem, v. 79, n. 2, p. 194-8, Mar 2003a. ISSN 1074-7427 (Print) 1074-7427.
 J.M. Zhuo; D. Pratico. Acceleration of brain amyloidosis in an Alzheimer's disease mouse model by a folate, vitamin B6 and B12-deficient diet. Exp Gerontol, v. 45, n. 3, p. 195-201, Mar 2010. ISSN 0531-5565
 S. Scarpa, A. Fuso, F. Dâ€™Anselmi, R. A. Cavallaro. Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease? FEBS Lett, v. 541, n. 1-3, p. 145-8, Apr 24 2003. ISSN 0014-5793 (Print) 0014-5793.
 A.D. Smith, S.M. Smith, C.A. Jager, P. Whitbread, C. Johnston, G. Agacinski, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One, v. 5, n. 9, p. e12244, 2010. ISSN 1932-6203.
 C.A. Jager, A. Oulhaj, R. Jacoby, H. Refsum, A. D. Smith. Cognitive and clinical outcomes of homocysteineâ€lowering Bâ€vitamin treatment in mild cognitive impairment: a randomized controlled trial. International journal of geriatric psychiatry, v. 27, n. 6, p. 592-600, 2012. https://doi.org/10.1002/gps.2758.
 J. Bryan, E. Calvaresi, D. Hughes. Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr, v. 132, n. 6, p. 1345-56, Jun 2002. ISSN 0022-3166 (Print) 0022-3166.
 S.J. Duthie, L.J. Whalley, A.R. Collins, S. Leaper, K. Berger, I.J. Deary. Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr, v. 75, n. 5, p. 908-13, May 2002. ISSN 0002-9165 (Print) 0002-9165.
 K.L. Harding, R.D. Judah, C.E. Gant. Outcome-based comparison of Ritalin versus food-supplement treated children with AD/HD. Altern Med Rev, v. 8, n. 3, p. 319-30, Aug 2003. ISSN 1089-5159 (Print) 1089-5159.
 J. Pellow, E.M. Solomon, C.N. Barnard. Complementary and alternative medical therapies for children with attention-deficit/hyperactivity disorder (ADHD). Altern Med Rev, v. 16, n. 4, p. 323-37, Dec 2011. ISSN 1089-5159 (Print) 1089-5159.
 J.F. Flood, M.L. Baker, J.L. Davis. Modulation of memory processing by glutamic acid receptor agonists and antagonists. Brain Research, v. 521, 1990. ISSN 1â€“2.
 D.E. Golan. Farmacologia da NeurotransmissÃ£o GABAÃ©rgica e GlutamatÃ©rgica. In: (Ed.). PrincÃpios de Farmacologia: A Base FisiopatolÃ³gica da Farmacoterapia. 2: EDITORA Guanabara Koogan S.A., 2009. Cap. 11, p.914. ISBN ISBN13: 9788527715201
 J.W. McDonald; M.V. Johnston. Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res Brain Res Rev, v. 15, n. 1, p. 41-70, Jan-Apr 1990. https://doi.org/10.1016/0165-0173(90)90011-C.
 Z. Xia, H. Dudek, C.K. Miranti, M.E. Greenberg. Calcium influx via the NMDA receptor induces immediate early gene transcription by a MAP kinase/ERK-dependent mechanism. J Neurosci, v. 16, n. 17, p. 5425-36, Sep 1 1996. ISSN 0270-6474 (Print) 0270-6474.
 S. Nakanishi. Molecular diversity of glutamate receptors and implications for brain function. Science, v. 258, n. 5082, p. 597-603, Oct 23 1992. ISSN 0036-8075 (Print) 0036-8075.
 M. Castagna, C. Shayakul, D. Trotti, V.F. Sacchi, W.R. Harvery, M.A. Hediger. Molecular characteristics of mammalian and insect amino acid transporters: implications for amino acid homeostasis. J Exp Biol, v. 200, n. Pt 2, p. 269-86, Jan 1997. ISSN 0022-0949 (Print) 0022-0949.
 Y. Kanai et al. A new family of neurotransmitter transporters: the high-affinity glutamate transporters. Faseb j, v. 7, n. 15, p. 1450-9, Dec 1994. ISSN 0892-6638 (Print) 0892-6638.
 Y. Kanai, C.P. Smith, M.A. Hediger. Family of neutral and acidic amino acid transporters: molecular biology, physiology and medical implications. Curr Opin Cell Biol, v. 9, n. 4, p. 565-72, Aug 1997. ISSN 0955-0674 (Print) 0955-0674.
 G.L. Collingridge; W. Singer. Excitatory amino acid receptors and synaptic plasticity. Trends in pharmacological sciences, v. 11, n. 7, p. 290-296, 1990. https://doi.org/10.1016/0165-6147(90)90011-V.
 C.W. Cotman; D.T. Monaghan. Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity.Annual review of neuroscience, v. 11, n. 1, p. 61-80, 1988. https://doi.org/10.1146/annurev.ne.11.030188.000425.
 F.F. Barbosa, J.R. Santos, Y.S.R. Meurer, P.T. Macedo, L.M.S. Ferreira, I.M.O. Pontes, et al. Differential Cortical c-Fos and Zif-268 Expression after Object and Spatial Memory Processing in a Standard or Episodic-Like Object Recognition Task. Front Behav Neurosci, v. 7, 2013.
 B. Bozon, S. Davis, S.Laroche. Regulated transcription of the immediate-early gene Zif268: mechanisms and gene dosage-dependent function in synaptic plasticity and memory formation. Hippocampus, v. 12, n. 5, p. 570-7, 2002. ISSN 1050-9631 (Print) 1050-9631.
 Q.R. Smith. Transport of glutamate and other amino acids at the blood-brain barrier. J Nutr, v. 130, n. 4S Suppl, p. 1016s-22s, Apr 2000. ISSN 0022-3166 (Print) 0022-3166.
 W.H. Oldendorf. Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. Am J Physiol, v. 221, n. 6, p. 1629-39, Dec 1971. ISSN 0002-9513 (Print) 0002-9513.
 W.H. Oldendorf; J. Szabo. Amino acid assignment to one of three blood-brain barrier amino acid carriers. Am J Physiol, v. 230, n. 1, p. 94-8, Jan 1976. ISSN 0002-9513 (Print) 0002-9513.
 W.M. Pardridge. Regulation of Amino Acid Availability to Brain: Selective Control Mechanisms For Glutamate. In: (Ed.). Glutamic Acid: Advances in Biochemistry and Physiology. New York: Raven Press, 1979. p.14.
 R.A. Hawkins, M.R. DeJoseph, P.A. Hawkins. Regional brain glutamate transport in rats at normal and raised concentrations of circulating glutamate. Cell Tissue Res, v. 281, n. 2, p. 207-14, Aug 1995. ISSN 0302-766X (Print) 0302-766x.
 P.M. Gross, R.G. Blasberg, J.D. Fenstemacher, C.S. Patlak. The microcirculation of rat circumventricular organs and pituitary gland. Brain Res Bull, v. 18, n. 1, p. 73-85, Jan 1987. ISSN 0361-9230 (Print) 0361-9230.
 P.M. Gross. Morphology and physiology of capillary systems in subregions of the subfornical organ and area postrema. Can J Physiol Pharmacol, v. 69, n. 7, p. 1010-25, Jul 1991. ISSN 0008-4212 (Print) 0008-4212.
 S.W. Shaver, J.J. Pang, D.S. Wainman, K.M. Wall, P.M. Gross. Morphology and function of capillary networks in subregions of the rat tuber cinereum. Cell Tissue Res, v. 267, n. 3, p. 437-48, Mar 1992. ISSN 0302-766X (Print) 0302-766x.
 M.T. Price et al. Uptake of exogenous glutamate and aspartate by circumventricular organs but not other regions of brain. J Neurochem, v. 36, n. 5, p. 1774-80, May 1981. ISSN 0022-3042 (Print) 0022-3042.
 M.T. Price, J.W. Olney, O.H. Lowry, S. Buchsbaum. Uptake of exogenous aspartate into circumventricular organs but not other regions of adult mouse brain. Journal of neurochemistry, v. 42, n. 3, p. 740-744, 1984. https://doi.org/10.1111/j.1471-4159.1984.tb02745.x.
 W. Vogel, D.M. Broverman, J.G. Draguns, E.L. Klaiber. The role of glutamic acid in cognitive behaviors.Psychological bulletin, v. 65, n. 6, p. 367, 1966. https://doi.org/10.1037/h0023351.
 E. Roberts; S. Frankel. Î³-aminobutyric acid in brain: its formation from glutamic acid. Journal of Biological Chemistry, v. 187, p. 55-63, 1950.
 A. Adler, I. Finkes, S. Katabi, Y. Prut, H. Bergman. Encoding by synchronization in the primate striatum. J. Neurosci. 33, 4854â€“4866 (2013) https://doi.org/10.1523/JNEUROSCI.4791-12.2013.
 T.N. Chase; C.A. Tamminga. GABA system participation in human motor, cognitive, and endocrine function. In: (Ed.). GABA-neurotransmitters: Munksgaard Copenhagen, 1979. p.283-294.
 B.E. Will, G. Toniolo, S. Brailowsky. Unilateral infusion of GABA and saline into the nucleus basalis of rats: 1. Effects on motor function and brain morphology. Behavioural brain research, v. 27, n. 2, p. 123-129, 1988. https://doi.org/10.1016/0166-4328(88)90038-1.
 F. Boy, J. Evans, R.A.E. Edden, K.D. Singh, M. Husain, P. Summer. Individual differences in subconscious motor control predicted by GABA concentration in SMA. Curr Biol, v. 20, n. 19, p. 1779-85, Oct 12 2010. ISSN 0960-9822.
 C.J. Stagg, V. Bachtiar, H. Johansen-Berg. The role of GABA in human motor learning. Curr Biol, v. 21, n. 6, p. 480-4, Mar 22 2011. ISSN 0960-9822.
 A. Floyer-Lea, M. Mlezinska, T. Kincses, P.M. Mattheuws. Rapid modulation of GABA concentration in human sensorimotor cortex during motor learning. J Neurophysiol, v. 95, n. 3, p. 1639-44, Mar 2006. ISSN 0022-3077 (Print) 0022-3077.
 I. Bar-Gad, G. Morris, H. Bergman. Information processing, dimensionality reduction and reinforcement learning in the basal ganglia. Prog Neurobiol, v. 71, n. 6, p. 439-73, Dec 2003. ISSN 0301-0082 (Print) 0301-0082.
 A. Bari; T.W. Robbins. Inhibition and impulsivity: behavioral and neural basis of response control. Prog Neurobiol, v. 108, p. 44-79, Sep 2013. ISSN 0301-0082.
 M.D. Humphries; T.J. Prescott. The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward. Prog Neurobiol, v. 90, n. 4, p. 385-417, Apr 2010. ISSN 0301-0082.
 D. Plenz. When inhibition goes incognito: feedback interaction between spiny projection neurons in striatal function. Trends Neurosci, v. 26, n. 8, p. 436-43, Aug 2003. ISSN 0166-2236 (Print)
 E. Roberts. GABAergic malfunction in the limbic system resulting from an aboriginal genetic defect in voltage-gated Na+-channel SCN5A is proposed to give rise to susceptibility to schizophrenia. Advances in pharmacology (San Diego, Calif.), v. 54, p. 119, 2006. https://doi.org/10.1016/S1054-3589(06)54006-2.
 E. Roberts. Roles of GABA in neurons in information processing in the vertebrate CNS. Neuronal information transfer, p. 213-239, 1978.
 E. Roberts. Disinhibition as an organizing principle in the nervous systemâ€”the role of the GABA system. Application to neurologic and psychiatric disorders. In: (Ed.). GABA in nervous system function: Raven Press New York, 1976. p.515-539.
 E. Roberts. Failure of GABAergic inhibition: a key to local and global seizures. Adv Neurol, v. 44, p. 319-41, 1986. ISSN 0091-3952 (Print) 0091-3952.
 E. Roberts. Living systems are tonically inhibited, autonomous optimizers, and disinhibition coupled to variability generation is their major organizing principle: inhibitory command-control at levels of membrane, genome, metabolism, brain, and society. Neurochem Res, v. 16, n. 3, p. 409-21, Mar 1991. ISSN 0364-3190 (Print) 0364-3190.
 L. Jasmin, S.D. Rabkin, A. Granato, A. Boudah, P.T. Ohara. Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex. Nature, v. 424, n. 6946, p. 316-20, Jul 17 2003. ISSN 0028-0836.
 S.P. Hunt; P.W. Mantyh. The molecular dynamics of pain control. Nat Rev Neurosci, v. 2, n. 2, p. 83-91, Feb 2001. ISSN 1471-003X (Print) 1471-003x.
 D.J. Nutt; A.L. Malizia. New insights into the role of the GABA (A)-benzodiazepine receptor in psychiatric disorder. Br J Psychiatry, v. 179, p. 390-6, Nov 2001. ISSN 0007-1250 (Print) 0007-1250.
 J. Bormann. The 'ABC' of GABA receptors. Trends Pharmacol Sci, v. 21, n. 1, p. 16-9, Jan 2000. ISSN 0165-6147 (Print) 0165-6147.
 E. Roberts. What do GABA neurons really do? They make possible variability generation in relation to demand. Exp Neurol, v. 93, n. 2, p. 279-90, Aug 1986b. ISSN 0014-4886 (Print) 0014-4886.
 J. Ong; D.I. Kerr. Recent advances in GABAB receptors: from pharmacology to molecular biology. Acta Pharmacol Sin, v. 21, n. 2, p. 111-23, Feb 2000. ISSN 1671-4083 (Print) 1671-4083.
 S.J. Zhang; M.B. Jackson. GABA-activated chloride channels in secretory nerve endings. Science, v. 259, n. 5094, p. 531-4, Jan 22 1993. ISSN 0036-8075 (Print) 0036-8075.
 K.J. Staley; I. Mody. Shunting of excitatory input to dentate gyrus granule cells by a depolarizing GABAA receptor-mediated postsynaptic conductance. J Neurophysiol, v. 68, n. 1, p. 197-212, Jul 1992. ISSN 0022-3077 (Print) 0022-3077.
 N. Shyamaladevi, A.R. Jayakumar, R. Sujatha, V. Paul, E.H. Subramanian. Evidence that nitric oxide production increases Î³-amino butyric acid permeability of blood-brain barrier. Brain research bulletin, v. 57, n. 2, p. 231-236, 2002. https://doi.org/10.1016/S0361-9230(01)00755-9.
 G.M. Knudsen, H.E. Poulsen, O.B. Paulson.. Blood-brain barrier permeability in galactosamine-induced hepatic encephalopathy. No evidence for increased GABA-transport. J Hepatol, v. 6, n. 2, p. 187-92, Apr 1988. ISSN 0168-8278 (Print) 0168-8278.
 M.L. Bassett, K.D. Mullen, B. Scholz, J.D.Fenstemacher, E.A. Jones. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy. Gastroenterology, v. 98, n. 3, p. 747-57, Mar 1990. ISSN 0016-5085 (Print) 0016-5085.
 G.M. Haig, H.N. Bockbrader, D.L. Wesche, S.W. Boellner, D. Ouellet, R.R. Brouwn, et al. Single-dose gabapentin pharmacokinetics and safety in healthy infants and children. J Clin Pharmacol, v. 41, n. 5, p. 507-14, May 2001. ISSN 0091-2700 (Print) 0091-2700.
 A. Yildiz, C. Quetscher, S. Dharmadhikari, W. Chmielewski, B. Glaubitz, T.S. Wilcke, et al. Feeling safe in the plane: neural mechanisms underlying superior action control in airplane pilot trainees--a combined EEG/MRS study. Hum Brain Mapp, v. 35, n. 10, p. 5040-51, Oct 2014. ISSN 1065-9471.
 L. Steenbergen, R. Sellaro, A.K. Stock, R. Beste, L. Colzato. Î³-Aminobutyric acid (GABA) administration improves action selection processes: a randomised controlled trial. Scientific Reports, 2015a.
 A.K. Stock, M. Blaszkewicz, c. Beste. Effects of binge drinking on action cascading processes: an EEG study. Arch Toxicol, v. 88, n. 2, p. 475-88, Feb 2014. ISSN 0340-5761.
 L. Steenbergen, R. Sellaro, A.K. Stock, B. Verkuill, C. Beste, L.S. Colzato. Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during action cascading processes. Eur Neuropsychopharmacol, v. 25, n. 6, p. 773-8, Jun 2015b. ISSN 0924-977x.
 V. Rizzo, A. Qiartarone, S. Bagnato, F. Battaglia, G. Majorana, P. Girlanda. Modification of cortical excitability induced by gabapentin: a study by transcranial magnetic stimulation. Neurol Sci, v. 22, n. 3, p. 229-32, Jun 2001. ISSN 1590-1874 (Print) 1590-1874.
 F. Verbruggen, D.W. Schneider, G.D. Logan. How to stop and change a response: the role of goal activation in multitasking.Journal of Experimental Psychology: Human Perception and Performance, v. 34, n. 5, p. 1212, 2008. https://doi.org/10.1037/0096-15184.108.40.2062.
 F. Stahl; G. Dorner. Responses of salivary cortisol levels to stress-situations. Endokrinologie, v. 80, n. 2, p. 158-62, Oct 1982. ISSN 0013-7251 (Print) 0013-7251.
 D.H. Hellhammer, C. Heib, W. Hubert, L. Rolf. Relationships between salivary cortisol release and behavioral coping under examination stress. IRCS Medical Science: Psychology & Psychiatry, v. 13, 1985.
 K.V. Jones, D.L. Copolov, K.H. Outch. Type A, test performance and salivary cortisol. Journal of Psychosomatic Research, v. 30, n. 6, 1986. ISSN 6.
 L. Martinek, K. Oberascher-Holzinger, S. Weishuhn, W. Klimesch, H.H. Kerschbaum. Anticipated academic examinations induce distinct cortisol responses in adolescent pupils. Neuro Endocrinol Lett, v. 24, n. 6, p. 449-53, Dec 2003. ISSN 0172-780X (Print) 0172-780x.
 M. Toda, R. Den, S. Nagasawa, K. Kitamura, K. Morimoto. Relationship between lifestyle scores and salivary stress markers cortisol and chromogranin A. Arch Environ Occup Health, v. 60, n. 5, p. 266-9, Sep-Oct 2005. ISSN 1933-8244 (Print) 1933-8244.
 D.T. O'Connor. Chromogranin: widespread immunoreactivity in polypeptide hormone producing tissues and in serum. Regul Pept, v. 6, n. 3, p. 263-80, Jul 1983. ISSN 0167-0115 (Print) 0167-0115.
 J. Saruta, K. Tsukinoki, K. Sasaguri, H. Ishii, M. Yasuda, Y.R. Osamura, et al. Expression and localization of chromogranin A gene and protein in human submandibular gland. Cells Tissues Organs, v. 180, n. 4, p. 237-44, 2005. ISSN 1422-6405 (Print) 1422-6405.
 T. Kanehira, Y. Nakamura, K. Nakamura, K. Horie, N. Horie, K. Furugori, et al. Relieving occupational fatigue by consumption of a beverage containing gamma-amino butyric acid. J Nutr Sci Vitaminol (Tokyo), v. 57, n. 1, p. 9-15, 2011. ISSN 0301-4800.
 A.M. Abdou, S. Higashiguchi, K. Horie, M. Kim, H. Hatta, H. Yokogoshi. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors, v. 26, n. 3, p. 201-8, 2006. ISSN 0951-6433 (Print) 0951-6433.
 P. Yang, G. Cai, Y. Cai, J. Fei, G. Liu. Gamma aminobutyric acid transporter subtype 1 gene knockout mice: a new model for attention deficit/hyperactivity disorder. Acta biochimica et biophysica Sinica, v. 45, n. 7, p. 578-585, 2013. https://doi.org/10.1093/abbs/gmt043.
 R.A. Edden, D. Crocetti, H. Zhu, D.L. Gilbert, S.H. Mostofsky. Reduced GABA concentration in attention- deficit/hyperactivity disorder. Arch Gen Psychiatry, v. 69, n. 7, p. 750-3, Jul 2012. ISSN 0003-990x.