Abstract #4650

Effects of astrocytic Nrf2 activation on recently-identified 13C and 1H MRS flux-based biomarkers of mitochondrial energetics and neurotransmitter cycling in Huntington's Disease

Golam M. I. Chowdhury¹, Peter Dixon², Robin de Graaf³, Xiaoxian Ma⁴, Johnson A Johnson⁵, Jeffrey A Johnson⁵, Larry Park⁶, Gerard Sanacora¹, Douglas L Rothman⁴, and Kevin L Behar¹

¹Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States, ²Department of Psychiatry, Yale University School of Medicine, ³Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, United States, ⁴Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, United States, ⁵School of Pharmacy, School of Pharmacy, University of Wisconsin, Madison, WI, United States, ⁶CHDI Management, CHDI Management/CHDI Foundation, Los Angeles, United States

Alterations in brain glucose and energy metabolism is observed in Huntington’s Disease (HD) and HD animal models. 1H-[13C]-MRS can be readily adapted to measure metabolic pathway flux by use of 13C-labeled substrates. In this study we assessed whether activation of the astroglial Nrf2-ARE pathway in the R6/2 mouse model of HD, which has shown therapeutic potential in HD animal models, can reverse the reduction in 13C labeling seen previously in R6/2 mice. In cortex and striatum, astroglial Nrf2 activation led to increased amino acid 13C labeling, suggesting a degree of improvement in mitochondrial and neurotransmitter fluxes in the R6/2 mice.

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