Regional brain metabolism in a murine systemic lupus erythematosus model

An Vo, Bruce T. Volpe, Chris C. Tang, Wynne K. Schiffer, Czeslawa Kowal, Patricio T. Huerta, Aziz M. Uluǧ, Stephen L. Dewey, David Eidelberg, Betty Diamond

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb- mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb- mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects.

Original languageEnglish (US)
Pages (from-to)1315-1320
Number of pages6
JournalJournal of Cerebral Blood Flow and Metabolism
Volume34
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • FDG-microPET
  • N-methyl-D-aspartate receptor
  • autoantibodies
  • behavior
  • stereological neuron count

Fingerprint Dive into the research topics of 'Regional brain metabolism in a murine systemic lupus erythematosus model'. Together they form a unique fingerprint.

  • Cite this

    Vo, A., Volpe, B. T., Tang, C. C., Schiffer, W. K., Kowal, C., Huerta, P. T., Uluǧ, A. M., Dewey, S. L., Eidelberg, D., & Diamond, B. (2014). Regional brain metabolism in a murine systemic lupus erythematosus model. Journal of Cerebral Blood Flow and Metabolism, 34(8), 1315-1320. https://doi.org/10.1038/jcbfm.2014.85