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

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Major Depressive Disorder (MDD) is linked to inflammation.
• In vivo preclinical models for studying inflammation-induced depression are limited.
• Whole-brain imaging is crucial for understanding MDD pathophysiology.

Purpose of the Study:

• To investigate brain changes associated with inflammation-induced depressive signs in rats.
• To utilize multimodal neuroimaging for a valid preclinical model of depression.
• To explore the role of glutamatergic pathways and astrocyte regulation.

Main Methods:

• An E. coli lipopolysaccharide (LPS) model was used to induce inflammation and depressive signs in rats.
• Multimodal neuroimaging (structural and metabolic) was employed.
• Striatal and hippocampal mRNA expression was analyzed.

Main Results:

• Acute LPS (2h) increased striatal glutamine and specific brain region volumes before depressive behaviors emerged.
• Depressive behaviors at 24h correlated with decreased striatal glutamine and regional volume normalization.
• Altered mRNA expression of glutamine homeostasis enzymes/transporters was observed in the striatum and hippocampus.

Conclusions:

• Inflammation-induced depressive behaviors involve dynamic changes in brain structure and metabolism.
• Astrocytic regulation of glutamine homeostasis is critical in inflammation-related depression.
• This study provides a valid preclinical model for evaluating anti-depressant strategies.