Nondopaminergic Neurotransmission in the Pathophysiology of Tourette Syndrome

Udvardi, Patrick T; Nespoli, Ester; Rizzo, Francesca Romana; Hengerer, Bastian; Ludolph, Andrea G.

doi:10.1016/b978-0-12-411546-0.00004-4

Cited by 35 publications

(15 citation statements)

References 112 publications

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“…This termination codon resulted from a guanine-to-adenosine transition at the nucleotide 951 position of the gene, leading to a complete loss of enzyme function. The HDC gene codes for the enzyme histidine decarboxylase, a rate-limiting enzyme in the biosynthesis of histamine from L-histidine [53]. These findings therefore suggested a potential role for HDC deficiency in the pathophysiology of TS through impairment of histamine neurotransmission.…”

Section: Clinical Studiesmentioning

confidence: 88%

“…Although the majority of studies have supported the role of dopamine in TS, there is growing evidence for alterations across multiple biochemical systems [51,52], including abnormal histaminergic neurotransmission [53]. Histamine is an organic nitrogenous compound that acts as a signaling molecule in the immune and gastrointestinal systems, as well as a neurotransmitter within the central nervous system [54].…”

Section: Dopaminergic and Histaminergic Pathways In Tourette Syndromementioning

confidence: 99%

“…A preliminary report from 1986 presented a small case series of three patients with TS where use of antihistaminergic agents exacerbated tics [84]. Caution is required when interpreting these findings, also in consideration of the non-selectivity There is evidence that histamine can directly control striatal neurons by affecting the activity of multiple neurotransmitters which are supposed to play a role alongside dopamine in the pathophysiology of TS [51][52][53]. Histamine can modulate the intrinsic electrical properties of striatal cholinergic interneurons and negatively regulate the release of GABA from striatal medium-spiny projection neurons by acting at the level of H3 heteroreceptors.…”

Section: Pharmacological Modulationmentioning

confidence: 99%

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Histaminergic modulation in Tourette syndrome

Cox

Seri

Cavanna

2016

Expert Opinion on Orphan Drugs

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Section: Clinical Studiesmentioning

confidence: 88%

Section: Dopaminergic and Histaminergic Pathways In Tourette Syndromementioning

confidence: 99%

Section: Pharmacological Modulationmentioning

confidence: 99%

See 1 more Smart Citation

Histaminergic modulation in Tourette syndrome

Cox

Seri

Cavanna

2016

Expert Opinion on Orphan Drugs

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“…Given that striatal interneurons exert a modulatory role on dopamine signaling (Ellender et al, 2011), this reduction is likely to contribute to the disinhibition of dopaminergic neurotransmission. The contribution of serotonin and norepinephrine in tics, albeit suggested by pharmacological evidence (see below), is more controversial and may be related to specific subgroups of TS and comorbid manifestations, rather than to the whole spectrum of tic disorders (Steeves and Fox, 2008; Udvardi et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

Animal models of tic disorders: A translational perspective

Godar

Mosher

Giovanni

et al. 2014

Journal of Neuroscience Methods

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Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders.

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“…Aripiprazole is a second generation antipsychotic drug (classical approach) that has been found to be effective on tic management and to have a well-tolerated side effect profile (Kawohl et al, 2009). It is known that dopamine metabolism is dysfunctional in GTS, but neuroimaging research, and genetic studies also implicate other neurotransmitters in tic generation: histamine, serotonin, noradrenaline, endocannabinoids, glutamate, and GABA (Buse et al, 2013; Udvardi et al, 2013). Since the glutamate and dopamine systems are closely connected, a newly proposed approach for GTS treatment consists of the glutamatergic modulator riluzole, which is known to exert neuroprotection from glutamate excito-toxicity both in vitro and in vivo (Risterucci et al, 2006).…”

Section: Animal Modelsmentioning

confidence: 99%

TS-EUROTRAIN: A European-Wide Investigation and Training Network on the Etiology and Pathophysiology of Gilles de la Tourette Syndrome

et al. 2016

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Gilles de la Tourette Syndrome (GTS) is characterized by the presence of multiple motor and phonic tics with a fluctuating course of intensity, frequency, and severity. Up to 90% of patients with GTS present with comorbid conditions, most commonly attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD), thus providing an excellent model for the exploration of shared etiology across disorders. TS-EUROTRAIN (FP7-PEOPLE-2012-ITN, Grant Agr.No. 316978) is a Marie Curie Initial Training Network (http://ts-eurotrain.eu) that aims to elucidate the complex etiology of the onset and clinical course of GTS, investigate the neurobiological underpinnings of GTS and related disorders, translate research findings into clinical applications, and establish a pan-European infrastructure for the study of GTS. This includes the challenges of (i) assembling a large genetic database for the evaluation of the genetic architecture with high statistical power; (ii) exploring the role of gene-environment interactions including the effects of epigenetic phenomena; (iii) employing endophenotype-based approaches to understand the shared etiology between GTS, OCD, and ADHD; (iv) establishing a developmental animal model for GTS; (v) gaining new insights into the neurobiological mechanisms of GTS via cross-sectional and longitudinal neuroimaging studies; and (vi) partaking in outreach activities including the dissemination of scientific knowledge about GTS to the public. Fifteen partners from academia and industry and 12 PhD candidates pursue the project. Here, we aim to share the design of an interdisciplinary project, showcasing the potential of large-scale collaborative efforts in the field of GTS. Our ultimate aims are to elucidate the complex etiology and neurobiological underpinnings of GTS, translate research findings into clinical applications, and establish Pan-European infrastructure for the study of GTS and associated disorders.

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Nondopaminergic Neurotransmission in the Pathophysiology of Tourette Syndrome

Cited by 35 publications

References 112 publications

Histaminergic modulation in Tourette syndrome

Histaminergic modulation in Tourette syndrome

Animal models of tic disorders: A translational perspective

TS-EUROTRAIN: A European-Wide Investigation and Training Network on the Etiology and Pathophysiology of Gilles de la Tourette Syndrome

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