TS-EUROTRAIN - Projects

Finding developmental aspects and possible drug targets of TS and OCD: metabotropic glutamatergic mechanisms in a neurodevelopmental rat model of repetitive behaviors (WP3)

Objectives: 1. Establish a developmental model of unilateral 6-OHDA lesion in rats in early developmental stages 2. Comparison of the repetitive behaviour induced by l-dopa application in the developmental and the adult model 3. Molecular analysis of lesion-induced changes  4. Test of tool compounds which modulate glutamatergic neurotransmission.

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Investigation of the molecular effects of glutamatergic drugs in vitro and in vivo (in a TS rat model and control animals) (WP3)

Objectives: 1. Establish a second rat model in comparison to the developmental model of unilateral 6-OHDA lesion in rats in early developmental stages (project 1) 2. Conduct behaviour studies and in vivo spectroscopic study in the small MRI animal core facility of the Ulm University Biocenter (BIU). 3. To investigate whether brain’s glutamate metabolism is influenced by medication with aripiprazole or riluzole. 4. Molecular analysis of different brain areas of the CSTC pre- and post-treatment.

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Studying glutamatergic function in in the frontal-striatal circuits in TS and OCD using N-Acetylcysteine (NAC) challenge: a Magnetic Resonance Spectroscopy (MRS) study in TS and OCD (WP3)

Objectives: 1.Investigate baseline glutamatergic concentrations in frontal-striatal circuits in TS and OCD patients, relative to controls. 2. Investigate glutamatergic changes after a single dose of 2400mg N-Acetylcysteine (NAC) in TS and OCD patients relative to controls. 3. Investigate relationships between glutamatergic changes in frontal/ striatal circuits and behavioral changes (tic/ OC symptom severity) in TS and OCD patients relative to controls. 4. Investigate relationships between glutamatergic pathway polymorphisms in TS and OCD and glutamatergic concentrations in frontal-striatal circuits, at baseline and after challenge with NAC (Data sharing with MHH and UULM).

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Glutamate metabolism in children, adolescents and adults with TS: a single voxel Magnetic Resonance Spectroscopy study (WP3)

Objectives: 1. Investigate levels of glutamate and its metabolites in TS patients compared to normal controls. 2. Investigate whether concentrations of glutamate metabolites are correlated to tic severity or to the existence and severity of comorbidities (ADHD and OCD). 3. Investigate whether brain’s glutamate metabolism is influenced by medication with aripiprazole. 4. Investigate whether treatment response to aripiprazole correlates to changes in the concentration of glutamate metabolites.

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