Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice

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• 作者：Liss ; ra Castellan Baldan ; Kyle聽A. Williams ; Jean-Dominique Gallezot ; Vladimir Pogorelov ; Maximiliano Rapanelli ; Michael Crowley ; George聽M. Anderson ; Erin Loring ; Roxanne Gorczyca ; Eileen Billingslea ; Suzanne Wasylink ; Kaitlyn聽E. Panza ; A.聽Gulhan Ercan-Sencicek ; Kuakarun Krusong ; Bennett聽L. Leventhal ; Hiroshi Ohtsu ; Michael聽H. Bloch ; Zo毛聽A. Hughes ; John聽H. Krystal ; Linda Mayes ; Ivan de聽Araujo ; et al.
• 刊名：Neuron
• 出版年：8 January, 2014
• 年：2014
• 卷：81
• 期：1
• 页码：77-90
• 全文大小：1748 K

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Summary

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.