Neuro-immune Interactions in Obsessive-Compulsive, Tourette’s, Attention-Deficit / Hyperactivity, and Autistic Spectrum disorders
Duration in months 48
Research project submitted, as pre-proposal, by Dr. Walter ADRIANI on 14/10/2014
Dopamine transporter (DAT) is expressed in the CNS but also in the periphery, on lymphocytes. The human DAT1 gene has a promoter VNTR polimorphism, associated with neuro-psychiatric disease (like ADHD, OCD, Tourette's, and autistic spectrum disorder). DAT protein, expressed in the periphery, participates in neuro-immune interactions. In agreement with the notion that auto-antibodies (aAbs, targeting self proteins) are increasingly being found in the blood of patients, we recently found elevated plasma anti-DAT titres in ADHD patients (unpublished), raising a possible role of auto-immunity and neuro-immune modulation in the pathogenesis of impulsivity-compulsivity.
This project will unravel the possible pathogenic role of plasma anti-DAT titres, and validate their use as a novel biomarker; in addition, we will dissect the contribution of DAT, expressed on lymphocytes, to neuro-immune modulation in interaction with the gut-brain axis. Further, we will (a) validate the clinical relevance of these mechanisms, in the frame of developmental, neuro-psychiatric disease, and (b) evaluate a combined probiotic formulation as a new therapeutic approach.
Specifically, we will focus on four major objectives:
1. Decipher molecular mechanisms responsible for production of anti-DAT titres and their interaction with lymphocytes, including consequences onto different types of immune cells.
2. Determine preclinically (in rodent models, with full behavioural phenotyping) the impact of anti-DAT titres, delivered peripherally or centrally, with a focus on production of impulsive-compulsive patterns.
3. Isolate the “extreme” behavioural traits (in rat models, using operant protocols tailored for impulsivity-compulsivity), to verify the relevance of (a) lymphocyte DAT-mediated signalling, (b) plasma anti-DAT titres, and (c) the (epi)genetics of neuro-immune regulation.
4. Conduct clinical studies on ADHD, OCD, Tourette’s, autistic spectrum disorder, and their comorbidities in children.
We have NOT been invited for second step (i.e. to submit a full proposal) ... Nobody will ever see whether these ideas were promising!
This project was not funded!
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