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J Comp Neurol. 2017 Nov 1;525(16):3476-3487. doi: 10.1002/cne.24279. Epub 2017 Aug 2.

Behavioral and stereological characterization of Hdc KO mice: Relation to Tourette syndrome.

Author information

1
Department of Anatomy and Neuroscience Center, University of Helsinki, Helsinki, Finland.
2
A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

Abstract

A premature termination codon in the human histidine decarboxylase (Hdc) gene has been identified in a family suffering from Guilles de la Tourette syndrome (GTS). In the current study we investigated if mice lacking the histamine producing enzyme HDC share the morphological and cytological phenotype with GTS patients by using magnetic resonance (MRI) and diffusion tensor imaging (DTI), unbiased stereology and immunohistochemistry. Behavior of Hdc knock-out (Hdc KO) mice was assessed in an open field test. The results of stereological, volumetric and DTI analysis measurements showed no significant differences between control and Hdc KO mice. The numbers and distribution of GABAergic parvalbumin or nitric oxide-expressing and cholinergic interneurons were normal in Hdc KO mice. Cortical morphology and layering in adult Hdc KO mice were also preserved. In open field test Hdc KO mice showed impaired exploratory activity and habituation when introduced to novel environment. Our results indicate that Hdc deficiency in mice does not disturb the development of striatal and cortical interneurons and does not lead to the morphological and cytological phenotypes characterized by humans with GTS. Nevertheless, histamine deficiency leads to behavioral alterations probably due to neurotransmitter dysbalance on the level of the striatum.

KEYWORDS:

AB_10000344; AB_2261231; GABA; RRID: AB_2079751; RRID: AB_887885; Tourette syndrome; acetylcholine; glutamate; histidine decarboxylase; parvalbumin; stereology; striatal interneurons

PMID:
28681514
DOI:
10.1002/cne.24279
[Indexed for MEDLINE]

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