Dynamic changes in microglia in the mouse hippocampus during administration and withdrawal of the CSF1R inhibitor PLX3397

Author:

Wang Qirun12,Wang Yi‐Yan12,Pu Wen‐Jun12,Ma Xiaohong12,Ni Rong‐Jun12ORCID

Affiliation:

1. Psychiatric Laboratory and Mental Health Center West China Hospital, Sichuan University Chengdu China

2. Sichuan Clinical Medical Research Center for Mental Disorders Chengdu China

Abstract

AbstractPexidartinib (PLX3397), a colony‐stimulating factor‐1 receptor (CSF1R) inhibitor, is currently in phase 1–3 clinical trials as a treatment for a variety of tumours. CSF1R signalling regulates the development, survival and maintenance of microglia, the resident brain innate immune cells. In this study, we examined the effects of PLX3397 in the drinking water of mice on microglia in the hippocampus using ionized calcium‐binding adapter molecule 1 (Iba1, a microglial marker) immunocytochemistry. A high concentration of PLX3397 (1 mg/mL) significantly decreased the density of Iba1‐immunoreactive cells after 7 days of exposure, but a low concentration of PLX3397 (0.5 mg/mL) did not. In addition, both low and high concentrations of PLX3397 significantly increased the intersection number, total length and maximum length of microglial processes in male mice. PLX3397 administered for 21 days eliminated microglia with 78% efficiency in males and 84% efficiency in females. Significant increases in microglial processes were found after both seven and 21 days of PLX3397 exposure in males, whereas decreases in microglial processes were observed after both 14 and 21 days of exposure in females. After PLX3397 withdrawal following its administration for 14 days in males, the soma size quickly returned to normal levels within a week. However, the microglial density, intersection number and total length of microglial processes after 3 days of recovery stabilized to untreated levels. In summary, these findings provide detailed insight into the dynamic changes in microglial number and morphology in the hippocampus in a dose‐ and time‐dependent manner after PLX3397 treatment and withdrawal.

Funder

Ministry of Science and Technology of the People's Republic of China

National Natural Science Foundation of China

Natural Science Foundation of Sichuan Province

Publisher

Wiley

Subject

Cell Biology,Developmental Biology,Molecular Biology,Ecology, Evolution, Behavior and Systematics,Histology,Anatomy

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