Publication Date

2014

Journal Title

Journal of Cerebral Blood Flow and Metabolism

Abstract

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and antinuclear 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.

Volume Number

34

Issue Number

8

Pages

1315-1320

Document Type

Article

EPub Date

2014/05/16

Status

Faculty; Northwell Researcher

Facility

School of Medicine; Northwell Health

Primary Department

Molecular Medicine

Additional Departments

Neurology

PMID

24824914

DOI

10.1038/jcbfm.2014.85


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