Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice

Oscar Solís, Jose Rubén García-Montes, Patricia Garcia-Sanz, Antonio S. Herranz, Maria José Asensio, Gina Kang, Noboru Hiroi, Rosario Moratalla

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Catechol-O-methyltransferase (COMT) degrades dopamine and its precursor L-DOPA and plays a critical role in regulating synaptic dopamine actions. We investigated the effects of heightened levels of COMT on dopamine-regulated motor behaviors and molecular alterations in a mouse model of dyskinesia. Transgenic mice overexpressing human COMT (TG) and their wildtype (WT) littermates received unilateral 6-OHDA lesions in the dorsal striatum and were treated chronically with L-DOPA for two weeks. L-DOPA-induced dyskinesia was exacerbated in TG mice without altering L-DOPA motor efficacy as determined by contralateral rotations or motor coordination. Inductions of FosB and phospho-acetylated histone 3 (molecular correlates of dyskinesia) were potentiated in the lesioned striatum of TG mice compared with their WT littermates. The TG mice had lower basal levels of dopamine in the striatum. In mice with lesions, L-DOPA induces a greater increase in the dopamine metabolite 3-methoxytyramine in the lesioned striatum of dyskinetic TG mice than in WT mice. The levels of serotonin and its metabolite were similar in TG and WT mice. Our results demonstrate that human COMT overexpression confers a heightened susceptibility to L-DOPA-induced dyskinesia and alters molecular and neurochemical responses in the lesioned striatum of mice.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalNeurobiology of Disease
Volume102
DOIs
StatePublished - Jun 1 2017

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Catechol O-Methyltransferase
Dyskinesias
Dopamine
Oxidopamine
Histones
Transgenic Mice
Serotonin

Keywords

  • 22q11.2
  • Abnormal involuntary movements
  • ARVCF
  • COMT
  • Dopamine
  • L-DOPA
  • LID
  • Striatum
  • TXNRD2

ASJC Scopus subject areas

  • Neurology

Cite this

Solís, O., García-Montes, J. R., Garcia-Sanz, P., Herranz, A. S., Asensio, M. J., Kang, G., ... Moratalla, R. (2017). Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice. Neurobiology of Disease, 102, 133-139. https://doi.org/10.1016/j.nbd.2017.03.006

Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice. / Solís, Oscar; García-Montes, Jose Rubén; Garcia-Sanz, Patricia; Herranz, Antonio S.; Asensio, Maria José; Kang, Gina; Hiroi, Noboru; Moratalla, Rosario.

In: Neurobiology of Disease, Vol. 102, 01.06.2017, p. 133-139.

Research output: Contribution to journalArticle

Solís, O, García-Montes, JR, Garcia-Sanz, P, Herranz, AS, Asensio, MJ, Kang, G, Hiroi, N & Moratalla, R 2017, 'Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice', Neurobiology of Disease, vol. 102, pp. 133-139. https://doi.org/10.1016/j.nbd.2017.03.006
Solís O, García-Montes JR, Garcia-Sanz P, Herranz AS, Asensio MJ, Kang G et al. Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice. Neurobiology of Disease. 2017 Jun 1;102:133-139. https://doi.org/10.1016/j.nbd.2017.03.006
Solís, Oscar ; García-Montes, Jose Rubén ; Garcia-Sanz, Patricia ; Herranz, Antonio S. ; Asensio, Maria José ; Kang, Gina ; Hiroi, Noboru ; Moratalla, Rosario. / Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice. In: Neurobiology of Disease. 2017 ; Vol. 102. pp. 133-139.
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