TS-EUROTRAIN - Projects

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.

Fellow ESR10
Host institution: University of Ulm
Duration: 36 months    
Supervisor: A. Ludolph, UULM; Co-supervisor: T.M. Böckers, K. Müller-Vahl, MHH; Seconding Company: BI PHARMA.

Tasks and methodology: In a joint venture between the Institute of Anatomy & Cell Biology, the Department of Child and Adolescent Psychiatry, and the recently founded „Boehringer Ingelheim Ulm University Biocenter“ (BIU) we investigate effects of psychotropic drugs in vitro and in vivo. In this project we want to examine the cell biological effects of orally administered aripiprazole – recently employed in TS, primarily a dopamine D2/3 and 5-HT1A partial agonist – and riluzole, a glutamate release modulator that will be investigated in a clinical trial in the US. Animal rodent model (dopamine D1 receptor stimulation in rats) of TS. Behaviour studies as in Project TRANSLATE-1 will be followed by an examination of cell biological effects of the applied substances in vivo first by non-invasive imaging (using the small MRI animal core facility of the BIU) to compare effects on the glutamatergic system with the results in project 4 of this WP3. Cell biology will be performed as per Project TRANSLATE-1 (Gene expression: rt-PCR, Protein level: HPLC, western blots and immunohistochemistry). The ESR will be part of a group of biologists and physicians and will work in the lab facilities of the Institute of Anatomy & Cell Biology together with other PhD students.

  • Task 1: Establish behaviour experiments in the TS rat model and control animals.
  • Task 2: Apply compounds orally over 3 weeks and measure behavioural effects
  • Task 3: Conduct MR spectroscopy studies in TS rat model and control animals before and after treatment.
  • Task 4: Analyse cell biological effects in different brain areas of the CSTC pre- and post-treatment.

Milestones: 1. Conduction of behaviour experiments in rat model of TS and control animals 2. Establish MR spectroscopy in rodents 3. Completion of MR spectroscopy before and after treatment 4. Results of cell biological investigation

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