Format

Send to

Choose Destination
See comment in PubMed Commons below
Neuron. 2014 Jan 8;81(1):77-90. doi: 10.1016/j.neuron.2013.10.052.

Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice.

Author information

1
Department of Psychiatry, Yale University School of Medicine.
2
Department of Child Study Center, Yale University School of Medicine.
3
Department of Diagnostic Radiology, Yale University School of Medicine.
4
Department of Laboratory Medicine, Yale University School of Medicine.
5
Department of Genetics, Yale University School of Medicine.
6
Department of Program on Neurogenetics, Yale University School of Medicine.
7
Neuroscience Research Unit, Pfizer, Inc., Cambridge, MA.
8
Dept. of Biochem., Faculty of Science, Chulalongkorn Univ., Bangkok, Thailand.
9
Nathan S. Kline Institute for Psychiatric Research.
10
New York University Dept of Child and Adolescent Psychiatry.
11
Tohoku University, Graduate School of Engineering, Sendai, Japan.
12
Department of Pediatrics, Yale University School of Medicine.
13
Department of Psychology, Yale University School of Medicine.
14
John B. Pierce Laboratory, New Haven, CT.
15
Integrated Neuroscience Research Program; New Haven, CT 06520.
#
Contributed equally

Erratum in

  • Neuron. 2014 Jun 4;82(5):1186-7.

Abstract

Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine (DA) D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal DA levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. DA D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm histidine decarboxylase deficiency as a rare cause of TS and identify HA-DA interactions in the basal ganglia as an important locus of pathology.

PMID:
24411733
PMCID:
PMC3894588
DOI:
10.1016/j.neuron.2013.10.052
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Support Center