| Literature DB >> 24411733 |
Kyle A Williams1,2, Jean-Dominique Gallezot3, Vladimir Pogorelov1, Lissandra Castellan Baldan1, Maximiliano Rapanelli1, Michael Crowley2, George M Anderson2,4, Erin Loring2,5,6, Roxanne Gorczyca7, Eileen Billingslea1, Suzanne Wasylink1, Kaitlyn E Panza2, A Gulhan Ercan-Sencicek2,5, Kuakarun Krusong1,8, Bennett L Leventhal9,10, Hiroshi Ohtsu11, Michael H Bloch1,2, Zoë A Hughes7, John H Krystal1, Linda Mayes1,2,12,13, Ivan de Araujo1,14, Yu-Shin Ding3, Matthew W State1,2,5,6, Christopher Pittenger1,2,13,15.
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.Entities:
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Year: 2014 PMID： 24411733 PMCID： PMC3894588 DOI： 10.1016/j.neuron.2013.10.052
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173