Inhibition of tumour necrosis factor alpha in the R6 and 2 mouse model of Huntington's disease by etanercept treatment

J Pido-Lopez, B Tanudjojo, S Farag, MK Bondulich et al

HuntingtonÕs Disease Centre, Department of Neurodegenerative Disease and UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK

Scientific Reports

HuntingtonÕs disease (HD) is an inherited neurodegenerative disorder caused by the expansion of the CAG repeat in exon 1 of the huntingtin (HTT) gene, which results in a mutant protein with an extended polyglutamine tract. Inflammation occurs in both the brain and the periphery of HD patients and mouse models, with increases in brain and/or plasma levels of neurotoxic TNF_ and several other proinflammatory cytokines. TNF_ promotes the generation of many of these cytokines, such as IL6, which raises the possibility that TNF_ is central to the inflammatory milieu associated with HD. A number of mouse studies have reported that the suppression of chronic immune activation during HD has beneficial consequences. Here, we investigated whether TNF_ contributes to the peripheral inflammation that occurs in the R6/2 mouse model, and whether the in vivo blockade of TNFalpha, via etanercept treatment, can modify disease progression. We found that etanercept treatment normalised the elevated plasma levels of some cytokines. This did not modify the progression of certain behavioural measures, but slightly ameliorated brain weight loss, possibly related to a reduction in the elevated striatal level of soluble TNFalpha.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)

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