PET evaluation of light-induced modulation of microglial activation and GLP-1R expression in depressive rats

Light therapy has been accepted as a promising therapeutic choice for depression. Positron emission tomography (PET) combined with specific radiotracers has great benefits for revealing pathogenesis and developing therapeutics. This study aimed to investigate the influences of light therapy on microglial activation and glucagon-like peptide-1 receptor (GLP-1R) expression in the brain of depressive rats using [¹⁸F]DPA-714 and [¹⁸F]exendin-4 PET. The results showed that chronic unpredictable mild stress (CUMS)-induced depressive rats had poorer performance in behavioral tests compared to normal rats (p < 0.05) and the depressive-like behavior could be ameliorated by light therapy. Besides, depressive rats had significantly higher [¹⁸F]DPA-714 uptake and lower [¹⁸F]FDG uptake compare to normal rats in 11 and 9 regions of interest (ROIs) of the brain, respectively (p < 0.05). After 5 weeks of light therapy, higher [¹⁸F]FDG and [¹⁸F]exendin-4 uptake was observed in most ROIs of light therapy-treated depressive rats compared to untreated depressive rats (p < 0.05) and no significant differences existed in [¹⁸F]DPA-714 uptake between the two groups. This study demonstrated that light therapy can ameliorate depressive-like behavior, improve glucose metabolism, and halt the decline of brain GLP-1R expression of depressive rats, but have no effects on microglial activation caused by CUMS. Besides, this study validated that [¹⁸F]DPA-714 and [¹⁸F]exendin-4 PET have the potential for noninvasive evaluation of microglial activation and GLP-1R expression in the brain of depression.