TY - JOUR

T1 - Structural and biochemical imaging reveals systemic LPS-induced changes in the rat brain

AU - Fritz, Michael

AU - Klawonn, Anna M

AU - Zhao, Qingyu

AU - Sullivan, Edith V

AU - Zahr, Natalie M

AU - Pfefferbaum, Adolf

N1 - Copyright © 2020 Elsevier B.V. All rights reserved.

PY - 2020

Y1 - 2020

N2 - Despite mounting evidence for the role of inflammation in Major Depressive Disorder (MDD), in vivo preclinical investigations of inflammation-induced negative affect using whole brain imaging modalities are scarce, precluding a valid model within which to evaluate pharmacological interventions. Here we used an E. coli lipopolysaccharide (LPS)-based model of inflammation-induced depressive signs in rats to explore brain changes using multimodal neuroimaging methods. During the acute phase of the LPS response (2 h post injection), prior to the emergence of a task-quantifiable depressive phenotype, striatal glutamine levels and splenial, retrosplenial, and peri-callosal hippocampal cortex volumes were greater than at baseline. LPS-induced depressive behaviors observed at 24 h, however, occurred concurrently with lower than control levels of striatal glutamine and a reversibility of volume expansion (i.e., shrinkage of splenial, retrosplenial, and peri-callosal hippocampal cortex to baseline volumes). In both striatum and hippocampus at 24 h, mRNA expression in LPS relative to control animals demonstrated alterations in enzymes and transporters regulating glutamine homeostasis. Collectively, the observed behavioral, in vivo structural and metabolic, and mRNA expression alterations suggest a critical role for astrocytic regulation of inflammation-induced depressive behaviors.

AB - Despite mounting evidence for the role of inflammation in Major Depressive Disorder (MDD), in vivo preclinical investigations of inflammation-induced negative affect using whole brain imaging modalities are scarce, precluding a valid model within which to evaluate pharmacological interventions. Here we used an E. coli lipopolysaccharide (LPS)-based model of inflammation-induced depressive signs in rats to explore brain changes using multimodal neuroimaging methods. During the acute phase of the LPS response (2 h post injection), prior to the emergence of a task-quantifiable depressive phenotype, striatal glutamine levels and splenial, retrosplenial, and peri-callosal hippocampal cortex volumes were greater than at baseline. LPS-induced depressive behaviors observed at 24 h, however, occurred concurrently with lower than control levels of striatal glutamine and a reversibility of volume expansion (i.e., shrinkage of splenial, retrosplenial, and peri-callosal hippocampal cortex to baseline volumes). In both striatum and hippocampus at 24 h, mRNA expression in LPS relative to control animals demonstrated alterations in enzymes and transporters regulating glutamine homeostasis. Collectively, the observed behavioral, in vivo structural and metabolic, and mRNA expression alterations suggest a critical role for astrocytic regulation of inflammation-induced depressive behaviors.

KW - Animals

KW - Brain/drug effects

KW - Depressive Disorder, Major/chemically induced

KW - Inflammation/chemically induced

KW - Lipopolysaccharides/toxicity

KW - Male

KW - Rats

KW - Rats, Inbred F344

U2 - 10.1016/j.jneuroim.2020.577367

DO - 10.1016/j.jneuroim.2020.577367

M3 - Journal article

C2 - 32866714

VL - 348

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

M1 - 577367

ER -