Role of GABAergic system in the pathogenesis and treatment of Tourette syndrome in children

XU Ying; SHI Haishui; ZHANG Huifeng; TIAN Xiaoyu

doi:10.11852/zgetbjzz2024-0307

PDF(510 KB)

Chinese Journal of Child Health Care ›› 2024, Vol. 32 ›› Issue (10) : 1101-1105. DOI: 10.11852/zgetbjzz2024-0307

Review

Role of GABAergic system in the pathogenesis and treatment of Tourette syndrome in children

XU Ying¹, SHI Haishui^2,3, ZHANG Huifeng¹, TIAN Xiaoyu¹

Author information +

History +

Abstract

Childhood Tourette syndrome(TS) is a chronic neuropsychiatric disorder with a prevalence of about 1% in children and adolescents. Its clinical features include sudden, involuntary twitching symptoms such as eye blinking, head shaking, and tics involving other muscles of the face, trunk, and limbs, as well as vocal tics. At present, the pathogenesis of TS is currently not clear, and there is no effective treatment for TS. γ-aminobotyric acid(GABA) is the primary inhibitory neurotransmitter in the mammalian brain. Some studies have shown that the imbalance of GABAergic system is involved in the occurrence and development of many neuropsychiatric diseases. In recent years, the role of GABAergic system in TS has gained much attention. Current research focuses on the abnormality of GABAergic metabolic pathway and the changes of GABA metabolism of intestinal flora in TS patients. However, there are no specific GABAergic drugs developed for the treatment of TS. This review provides insights into the role of the GABAergic system in the pathophysiology of TS and its potential as a novel therapeutic target.

Key words

Tourette syndrome / γ-aminobotyric acid / GABAergic system / brain-gut axis

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

XU Ying, SHI Haishui, ZHANG Huifeng, TIAN Xiaoyu. Role of GABAergic system in the pathogenesis and treatment of Tourette syndrome in children[J]. Chinese Journal of Child Health Care. 2024, 32(10): 1101-1105 https://doi.org/10.11852/zgetbjzz2024-0307

References

[1] Robertson NP. Advances in Tourette′s syndrome[J]. J Neurol, 2023, 270(3): 1808-1810.
[2] Yu D, Sul JH, Tsetsos F, et al. Interrogating the genetic determinants of Tourette′s syndrome and other tic disorders through genome-wide association studies[J]. Am J Psychiatry, 2019, 176(3): 217-227.
[3] Mahjani B, Bey K, Boberg J, et al. Genetics of obsessive-compulsive disorder[J]. Psychol Med, 2021, 51(13): 2247-2259.
[4] Pedersen JH, Skytthe A, Bybjerg-Grauholm J, et al. Concordance and comorbidities among monozygotic twins with tic disorders[J]. J Psychiatr Res, 2022, 146: 297-303.
[5] Wang X, Liu X, Chen L, et al. The inflammatory injury in the striatal microglia-dopaminergic-neuron crosstalk involved in Tourette syndrome development[J]. Front Immunol, 2023, 14: 1178113.
[6] Israelashvili M, Yael D, Vinner E, et al. Common neuronal mechanisms underlying tics and hyperactivity[J]. Cortex, 2020, 127: 231-247.
[7] Schilke E D, Tremolizzo L, Appollonio I, et al. Tics: Neurological disorders determined by a deficit in sensorimotor gating processes[J]. Neurol Sci, 2022, 43(10): 5839-5850.
[8] Chen M, Ruan G, Chen L, et al. Neurotransmitter and intestinal interactions: Focus on the microbiota-gut-brain axis in irritable bowel syndrome[J]. Front Endocrinol (Lausanne), 2022, 13: 817100.
[9] Peerboom C, Wierenga C J. The postnatal GABA shift: A developmental perspective[J]. Neurosci Biobehav Rev, 2021, 124: 179-192.
[10] Luscher B, Maguire J L, Rudolph U, et al. GABA(A) receptors as targets for treating affective and cognitive symptoms of depression[J]. Trends Pharmacol Sci, 2023, 44(9): 586-600.
[11] Koh W, Kwak H, Cheong E, et al. GABA tone regulation and its cognitive functions in the brain[J]. Nat Rev Neurosci, 2023, 24(9): 523-539.
[12] Sears SM, Hewett SJ. Influence of glutamate and GABA transport on brain excitatory/inhibitory balance[J]. Exp Biol Med (Maywood), 2021, 246(9): 1069-1083.
[13] Tanaka K. Astroglia and obsessive compulsive disorder[J]. Adv Neurobiol, 2021, 26: 139-149.
[14] Johnson KA, Worbe Y, Foote KD, et al. Tourette syndrome: clinical features, pathophysiology, and treatment[J]. Lancet Neurol, 2023, 22(2): 147-158.
[15] Favuzzi E, Huang S, Saldi GA, et al. GABA-receptive microglia selectively sculpt developing inhibitory circuits[J]. Cell, 2021, 184(15): 4048-4063.e32.
[16] Cothros N, Medina A, Pringsheim T. Current pharmacotherapy for tic disorders[J]. Expert Opin Pharmacother, 2020, 21(5): 567-580.
[17] Shitovaa D, Zharikova TS, Kovaleva ON, et al. Tourette syndrome and obsessive-compulsive disorder: A comprehensive review of structural alterations and neurological mechanisms[J]. Behav Brain Res, 2023, 453: 114606.
[18] Israelashvili M, Yael D, Vinner E, et al . Common neuronal mechanisms underlying tics and hyperactivity[J]. Cortex, 2020,127:231-247.
[19] Worbe Y, Marrakchi-Kacem L, Lecomte S, et al. Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome[J]. Brain, 2015, 138(Pt 2): 472-482.
[20] Lennington JB, Coppola G, Kataoka-Sasaki Y, et al. Transcriptome analysis of the human striatum in Tourette syndrome[J]. Biol Psychiatry, 2016, 79(5): 372-382.
[21] Barbour AJ, Gourmaud S, Lancaster E, et al. Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer′s disease and 5XFAD mice[J]. Brain, 2024,147(6):2169-2184.
[22] Zhang W, Yu W, Liu X, et al. Effect of Jian-Pi-Zhi-Dong decoction on the amino acid neurotransmitters in a rat model of Tourette syndrome and comorbid anxiety disorder[J]. Front Psychiatry, 2020, 11: 515.
[23] Xiao L, Priest MF, Nasenbeny J, et al. Biased oxytocinergic modulation of midbrain dopamine systems[J]. Neuron, 2017, 95(2): 368-384.e5.
[24] Cadeddu R, Knutson DE, Mosher LJ, et al. The α6 GABA(A) receptor positive allosteric modulator DK-I-56-1 reduces tic-related behaviors in mouse models of Tourette syndrome[J]. Biomolecules, 2021,11(2):175.
[25] Draper A, Stephenson MC, Jackson GM, et al. Increased GABA contributes to enhanced control over motor excitability in Tourette syndrome[J]. Curr Biol, 2014, 24(19): 2343-2347.
[26] 于文静,白雪,张雯,等.健脾止动汤对多发性抽动症患儿神经递质的影响[J].中华中医药杂志,2015,30(5):1757-1761.
Yu WJ, Bai X, Zhang W, et al. Effect of spleen-enhancing and stopping action soup on neurotransmitters in children with multiple tic disorders[J]. Chinese Medicine Miscellany, 2015,30(5):1757-1761.(in Chinese)
[27] Liu S, Tian M, He F, et al. Mutations in ASH1L confer susceptibility to Tourette syndrome[J]. Mol Psychiatry, 2020, 25(2): 476-490.
[28] Qin L, Williams JB, Tan T, et al. Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures[J]. Nat Commun, 2021, 12(1): 6589.
[29] Tsetsos F, Yu D, Sul JH, et al. Synaptic processes and immune-related pathways implicated in Tourette syndrome[J]. Transl Psychiatry, 2021, 11(1): 56.
[30] Dicks LMT. Gut Bacteria and neurotransmitters[J]. Microorganisms, 2022,10(9):1838.
[31] Serrano-Castro P J, Rodríguez-Uranga JJ, Cabezudo-García P, et al. Cenobamate and clobazam combination as personalized medicine in autoimmune-associated epilepsy with anti-Gad65 antibodies[J]. Neurol Neuroimmunol Neuroinflamm,2023,10(6):e200151.
[32] Liao Y, Fan L, Bin P, et al. GABA signaling enforces intestinal germinal center B cell differentiation[J]. Proc Natl Acad Sci U S A, 2022, 119(44): e2215921119.
[33] Zhao H, Shi Y, Luo X, et al. The effect of fecal microbiota transplantation on a child with Tourette syndrome[J]. Case Rep Med, 2017, 2017: 6165239.
[34] Xi W, Gao X, Zhao H, et al. Depicting the composition of gut microbiota in children with tic disorders: An exploratory study[J]. J Child Psychol Psychiatry, 2021, 62(10): 1246-1254.
[35] Sanchez M, Fernández J, Martin M, et al. Purification and properties of two succinic semialdehyde dehydrogenases from Klebsiella pneumoniae[J]. Biochim Biophys Acta, 1989, 990(3): 225-231.
[36] Strandwitz P, Kim KH, Terekhova D, et al. GABA-modulating bacteria of the human gut microbiota[J]. Nat Microbiol, 2019, 4(3): 396-403.
[37] Yunes RA, Poluektovae U, Dyachkovam S, et al. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota[J]. Anaerobe, 2016, 42: 197-204.
[38] Hartmann A. Clinical pharmacology of nondopaminergic drugs in Tourette syndrome[J]. Int Rev Neurobiol, 2013, 112: 351-372.
[39] Awaad Y. Tics in Tourette syndrome: New treatment options[J]. J Child Neurol, 1999, 14(5): 316-319.
[40] Singer HS, Wendlandt J, Krieger M, et al. Baclofen treatment in Tourette syndrome: A double-blind, placebo-controlled, crossover trial[J]. Neurology, 2001, 56(5): 599-604.
[41] Giyyis AH, Leventhal DK, Fensterheim BA, et al. Selective inhibition of striatal fast-spiking interneurons causes dyskinesias[J]. J Neurosci, 2011, 31(44): 15727-15731.
[42] 胡屹伟,巩利,李林文.肌苷和γ-氨基丁酸治疗抽动-秽语综合征疗效观察[J].山东医药,1995,39(7):12.
Hu YW,Gong L,Li LW. Observation on the efficacy of inosine and gamma-aminobutyric acid in the treatment of Tourette′s syndrome[J]. Shandong Medicine,1995,39(7):12.(in Chinese)