Regional brain metabolism in a murine systemic lupus erythematosus model.
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.
Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
An
A
Vo
Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Bruce T
BT
Volpe
Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Chris C
CC
Tang
Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Wynne K
WK
Schiffer
Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Czeslawa
C
Kowal
Laboratory of Immune & Neural Networks, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Patricio T
PT
Huerta
Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Aziz M
AM
Uluğ
Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Stephen L
SL
Dewey
Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
David
D
Eidelberg
Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Betty
B
Diamond
D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism*; D001522:Behavior, Animal; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography
D000974:Antibodies, Antinuclear; D019788:Fluorodeoxyglucose F18