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

Academic Article

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. © 2014 Elsevier Inc.
  • Published In

  • Neuron  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 17227561
  • Author List

  • Castellan Baldan L; Williams KA; Gallezot JD; Pogorelov V; Rapanelli M; Crowley M; Anderson GM; Loring E; Gorczyca R; Billingslea E
  • Start Page

  • 77
  • End Page

  • 90
  • Volume

  • 81
  • Issue

  • 1