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Molecular Imaging of Serotonin Synthesis in the Brain

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Targeting the Broadly Pathogenic Kynurenine Pathway

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Abstract

Tracer kinetic analysis of 11C-labeled alpha-methyl-tryptophan (AMT) allows quantitative assessment of serotonin synthesis using positron emission tomography (PET) imaging in human brain. The obtained K-complex represents an index of serotonin synthesis (termed serotonin synthesis capacity) that is well suited to study serotonergic mechanisms in the developing brain. Assessment of global and local developmental changes of serotonin synthesis capacity in brains of autistic children indicates impaired serotonin metabolism that affects neuronal differentiation of serotonergic neurons during critical developmental periods. Moreover, increased serotonin synthesis capacity in various supratentorial regions of children with alternating hemiplegia is observed during ictal and postictal periods, suggesting increased regional serotonergic activity associated with hemiplegic attacks in extended neural networks. Finally, children with Tourette syndrome show decreased serotonin synthesis capacity in the bilateral dorsolateral prefrontal cortex and increased serotonin synthesis capacity in the bilateral thalamus and caudate, suggesting abnormal tryptophan metabolism in the fronto-striato-thalamic circuits.

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Abbreviations

5-HIAA:

5-Hydroxyindoleacetic acid

5-RIAA:

5-Hydroxyindole acetic acid

ADHD:

Attention-deficit hyperactivity disorder

AMHT:

Alpha-methyl-5-hydroxytryptophan

AMS:

Alpha-methylserotonin

AMT:

Alpha-[11C]methyl-l-tryptophan

OCD:

Obsessive-compulsive disorder

PET:

Positron emission tomography

TS:

Tourette syndrome

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Author information

Authors and Affiliations

  1. Department of Pediatrics, Wayne State University, Detroit, MI, 48201, USA

    Otto Muzik Ph.D. & Csaba Juhász M.D., Ph.D.

  2. Department of Radiology, Wayne State University, Detroit, MI, 48201, USA

    Otto Muzik Ph.D.

  3. PET Center, Children’s Hospital of Michigan, 3901 Beaubien St., Detroit, MI, 48201, USA

    Otto Muzik Ph.D.

  4. Department of Neurosurgery, Wayne State University, Detroit, MI, 48201, USA

    Sandeep Mittal M.D., F.R.C.S.C., F.A.C.S.

  5. Department of Oncology, Wayne State University, Detroit, MI, 48201, USA

    Sandeep Mittal M.D., F.R.C.S.C., F.A.C.S.

  6. Department of Neurology, Wayne State University, Detroit, MI, 48201, USA

    Csaba Juhász M.D., Ph.D.

Authors
  1. Otto Muzik Ph.D.
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  2. Sandeep Mittal M.D., F.R.C.S.C., F.A.C.S.
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  3. Csaba Juhász M.D., Ph.D.
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Corresponding author

Correspondence to Otto Muzik Ph.D. .

Editor information

Editors and Affiliations

  1. Chairman, Department of Neurosurgery, Wayne State University, Detroit, Michigan, USA

    Sandeep Mittal

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Muzik, O., Mittal, S., Juhász, C. (2015). Molecular Imaging of Serotonin Synthesis in the Brain. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_27

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