Electroconvulsive shock ameliorates disease processes and extends survival in huntingtin mutant mice

Mohamed R. Mughal, Akanksha Baharani, Srinivasulu Chigurupati, Tae Gen Son, Edmund Chen, Peter Yang, Eitan Okun, Thiruma Arumugam, Sic L. Chan, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by expanded polyglutamine repeats in the huntingtin (Htt) protein. Mutant Htt may damage and kill striatal neurons by a mechanism involving reduced production of brain-derived neurotrophic factor (BDNF) and increased oxidative and metabolic stress. Because electroconvulsive shock (ECS) can stimulate the production of BDNF and protect neurons against stress, we determined whether ECS treatment would modify the disease process and provide a therapeutic benefit in a mouse model of HD. ECS (50 mA for 0.2 s) or sham treatment was administered once weekly to male N171-82Q Htt mutant mice beginning at 2 months of age. Endpoints measured included motor function, striatal and cortical pathology, and levels of protein chaperones and BDNF. ECS treatment delayed the onset of motor symptoms and body weight loss and extended the survival of HD mice. Striatal neurodegeneration was attenuated and levels of protein chaperones (Hsp70 and Hsp40) and BDNF were elevated in striatal neurons of ECS-treated compared with sham-treated HD mice. Our findings demonstrate that ECS can increase the resistance of neurons to mutant Htt resulting in improved functional outcome and extended survival. The potential of ECS as an intervention in subjects that inherit the mutant Htt gene merits further consideration. Published by Oxford University Press 2010.

Original languageEnglish (US)
Article numberddq512
Pages (from-to)659-669
Number of pages11
JournalHuman Molecular Genetics
Volume20
Issue number4
DOIs
StatePublished - Feb 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

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