Phosphodiesterase 10 inhibition reduces striatal excitotoxicity in the quinolinic acid model of Huntington's disease

Carmela Giampà, Stefano Patassini, Antonella Borreca, Daunia Laurenti, Fabrizia Marullo, Giorgio Bernardi, Frank S. Menniti, Francesca R. Fusco

Research output: Contribution to journalArticle

Abstract

Decreased activity of cAMP responsive element-binding protein (CREB) is thought to contribute to the death of striatal medium spiny neurons in Huntington's disease (HD). Therefore, therapies that increase levels of activated CREB, may be effective in fighting neurodegeneration in HD. In this study, we sought to determine whether the phosphodiesterase type 10 (PDE10A) inhibitor TP10 exerts a neuroprotective effect in an excitotoxic model of HD. Rats were surgically administered with quinolinic acid into striatum and subsequently treated with TP10 daily for two or eight weeks. After 2 weeks of TP10 treatment, striatal lesion size was 52% smaller and the surviving cell number was several times higher than in the vehicle-treated group. These beneficial effects of TP10 were maintained through 8 weeks. TP10 treatment also increased significantly the levels of activated CREB in the striatal spiny neurons, which is hypothesized to be a contributing mechanism for the neuroprotective effect. Our findings suggest PDE10A inhibition as a novel neuroprotective approach to the treatment of HD and confirm the importance of phosphodiesterase inhibition in fighting the disease.

Original languageEnglish
Pages (from-to)450-456
Number of pages7
JournalNeurobiology of Disease
Volume34
Issue number3
DOIs
Publication statusPublished - Jun 2009

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Quinolinic Acid
Corpus Striatum
Huntington Disease
Phosphoric Diester Hydrolases
Carrier Proteins
Neuroprotective Agents
Neurons
Cell Count
Inhibition (Psychology)

Keywords

  • Huntington's disease
  • Immunohistochemistry
  • PDE inhibitors
  • Rat
  • Striatum

ASJC Scopus subject areas

  • Neurology

Cite this

Phosphodiesterase 10 inhibition reduces striatal excitotoxicity in the quinolinic acid model of Huntington's disease. / Giampà, Carmela; Patassini, Stefano; Borreca, Antonella; Laurenti, Daunia; Marullo, Fabrizia; Bernardi, Giorgio; Menniti, Frank S.; Fusco, Francesca R.

In: Neurobiology of Disease, Vol. 34, No. 3, 06.2009, p. 450-456.

Research output: Contribution to journalArticle

Giampà, C, Patassini, S, Borreca, A, Laurenti, D, Marullo, F, Bernardi, G, Menniti, FS & Fusco, FR 2009, 'Phosphodiesterase 10 inhibition reduces striatal excitotoxicity in the quinolinic acid model of Huntington's disease', Neurobiology of Disease, vol. 34, no. 3, pp. 450-456. https://doi.org/10.1016/j.nbd.2009.02.014
Giampà, Carmela ; Patassini, Stefano ; Borreca, Antonella ; Laurenti, Daunia ; Marullo, Fabrizia ; Bernardi, Giorgio ; Menniti, Frank S. ; Fusco, Francesca R. / Phosphodiesterase 10 inhibition reduces striatal excitotoxicity in the quinolinic acid model of Huntington's disease. In: Neurobiology of Disease. 2009 ; Vol. 34, No. 3. pp. 450-456.
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