Neuron · 2014
Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАVideo-Audio MediaНазвание и аннотация: Перевод в очереди
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Baldan Lissandra Castellan, Williams Kyle A, Gallezot Jean-Dominique, Pogorelov Vladimir, Rapanelli Maximiliano, Crowley Michael, Anderson George M, Loring Erin, Gorczyca Roxanne, Billingslea Eileen, Wasylink Suzanne, Panza Kaitlyn E, Ercan-Sencicek A Gulhan, Krusong Kuakarun, Leventhal Bennett L, Ohtsu Hiroshi, Bloch Michael H, Hughes Zoë A, Krystal John H, Mayes Linda, de Araujo Ivan, Ding Yu-Shin, State Matthew W, Pittenger Christopher
Аннотация
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.