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Article Dans Une Revue Neurobiology of Disease Année : 2012

NP03, a novel low-dose lithium formulation, is neuroprotective in the YAC128 mouse model of Huntington disease

Mahmoud A. Pouladi
  • Fonction : Auteur
Elsa Brillaud
  • Fonction : Auteur
Yuanyun Xie
  • Fonction : Auteur
Paola Conforti
  • Fonction : Auteur
Rona K. Graham
  • Fonction : Auteur
Dagmar E. Ehrnhoefer
  • Fonction : Auteur
Sonia Franciosi
  • Fonction : Auteur
Weining Zhang
  • Fonction : Auteur
Patrick Poucheret
  • Fonction : Auteur
Elsa Compte
  • Fonction : Auteur
Jean-Claude Maurel
  • Fonction : Auteur
Chiara Zuccato
  • Fonction : Auteur
Elena Cattaneo
  • Fonction : Auteur
Christian Neri
Michael R. Hayden
  • Fonction : Auteur

Résumé

Huntington disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene, remains without a treatment to modify the course of the illness. Lithium, a drug widely used for the treatment of bipolar disorder, has been shown to exert neuroprotective effects in a number of models of neurological disease but may have various toxic effects at conventional therapeutic doses. We examined whether NP03, a novel low-dose lithium microemulsion, would improve the disease phenotypes in the YAC128 mouse model of HD. We demonstrate that NP03 improves motor function, ameliorates the neuropathological deficits in striatal volume, neuronal counts, and DARPP-32 expression, and partially rescues testicular atrophy in YAC128 mice. These positive effects were accompanied by improvements in multiple biochemical endpoints associated with the pathogenesis of HD, including normalization of caspase-6-activation and amelioration of deficits in BDNF levels, and with no lithium-related toxicity. Our findings demonstrate that NP03 ameliorates the motor and neuropathological phenotypes in the YAC128 mouse model of HD, and represents a potential therapeutic approach for HD.
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Dates et versions

hal-01545519 , version 1 (22-06-2017)

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Citer

Mahmoud A. Pouladi, Elsa Brillaud, Yuanyun Xie, Paola Conforti, Rona K. Graham, et al.. NP03, a novel low-dose lithium formulation, is neuroprotective in the YAC128 mouse model of Huntington disease. Neurobiology of Disease, 2012, 48 (3), pp.282-289. ⟨10.1016/j.nbd.2012.06.026⟩. ⟨hal-01545519⟩
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