Dimitri Brinet (Presenter)
Sahlgrenka Academy at Gothenburg University
Bio: Dimitri Brinet is a trained analytical-chemist who studied at premier French research institutions (Sorbonne Paris-Descartes and Curie Inst.). He received his Phd in 2015 under the supervision of Prof Myriam Taverna and Prof Sandrine Ongeri at University of Paris-Sud. During his PhD he developed several tools to monitor the amyloid β peptide oligomerization. These innovative method mainly based on capillary electrophoresis allows an interesting evaluation of compounds against Alzheimer's disease on the initial stages of Aβ aggregation. Few months ago, he joined the Neurochemistry group at Sahlgrenska Academy at Gothenburg University as postdoctoral researcher. Under the supervision of Dr. Jörg Hanrieder, he is developing several bioanalytical strategies to improve the diagnosis of brain diseases. These methods are based on different interdisciplinary approaches but mostly on MS.
Authorship: Dimitri Brinet (1,2), and Sandra Engerberg (2) and Jörg Hanrieder* (1,2,3)
(1) University of Gothenburg, Mölndal, Sweden; (2) Chalmers University of Technology, Gothenburg, Sweden; (3) University College London, London, UK
| Short Abstract Psychiatric disorders such as depression and bipolarity are leading causes of disability and have huge socioeconomic consequences. The molecular mechanisms underlying psychiatric diseases still remain elusive. Pharmacotherapy of these conditions aim at modulating the neurotransmitter equilibrium in the synaptic cleft. However, appropriate molecular markers to monitor psycho-pharmacotherapy effects are not available. We developed a SPE-LCMS method for quantification of neurotransmitters in CSF. Neurotransmitter quantification was employed to establish comprehensive CSF profiles in suicidal patients that underwent psychopharmaca treatment. The data aid to improve diagnosis, prognosis of psychiatric conditions as well as monitor treatment effects and provide insight in the underlying molecular pathology. |
Long Abstract
Introduction
Psychiatric disorders such as depression and bipolarity are leading causes of disability worldwide, and have a huge societal impact. Despite the clear need for better diagnosis and understanding of the molecular basis of these disorders, the implemented means are not sufficient to satisfy the entire clinical requirements. A multidisciplinary approach will be crucial in addressing this problem.
These central nervous system (CNS) disorders involve abnormalities in key neurotransmitter signaling systems. An accurate follow-up of these biomarkers which continue to change during disease progression could be used as pharmacodynamic measures in clinical trials, also aid in the diagnosis and treatment of these disorders. Since the brain is not directly accessible for molecular in vivo investigation, cerebrospinal fluid (CSF) is a well suited specimen to monitor neuropathology as it contains soluble components providing insights into normal and pathologic processes. CSF provides therefore an accessible liquid to directly study biochemical brain disturbances in a minimally invasive way.
Thus, there is a great need to develop sensitive and reliable methods for profiling the entire neurotransmitter profile from CSF individuals with psychiatric disorders. These profiles can serve as diagnostic markers of psychiatric conditions. Moreover they can be used to monitor psychoparmaca treatment effects and allow improved prognosis and outcome prediction.
Method
We present an easy to implement strategy based on Mass Spectrometry (MS) coupled to Liquid Chromatography (LC) following mixed mode solid phase extraction to investigate biogenic amine profiles of CSF in neuropsychiatric disorders
Catecholamines were extracted from CSF by mixed mode solid-liquid extraction followed by primary amine derivatization. Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was used for quantification.
Results
We developed a targeted-neurotransmitter, Selected Reaction Monitoring (SRM) assay for the absolute quantitation of several catecholamines in the same time. Using adequate sample preparation, allowed comprehensive neurotransmitter’s profiling in CSF. Preliminary results have been to quantify biomarkers in CSF collected from psychiatric diseases and control individuals.
Conclusion
The need for an easy, robust and early diagnosis of several non-curable brain diseases is still unmet. In addition, biomarkers are also needed to monitor progression of disease in diagnosed patients. Our method enabled the exploration of relationships between neurotransmitter’s profile and the brain disease. It is providing a robust approach with relatively rapid assay development. Our results represent a comprehensive characterization of catecholamines CSF composition. This CSF profiling would establish a comparative standard method for investigations into a variety of diseases with neurological and psychiatric features.
References & Acknowledgements:
This work was supported by the the Swedish Research Council (VR) and U.S. National Institutes of Health (NIH)
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