Effect of infiltration of peripheral monocytes in the hippocampal CA3 region on neuralgia and the anxiety-like behavior in mice
10.16098/j.issn.0529-1356.2024.06.003
- VernacularTitle:外周单核细胞海马CA3区浸润对小鼠神经痛及焦虑样行为的影响
- Author:
Jia-Le DAI
1
;
Ying-Jun LIU
;
Xiao-Mei SHAO
;
Jian-Qiao FANG
;
Fang FANG
Author Information
1. 浙江中医药大学第三临床医学院,浙江省针灸神经病学重点实验室,杭州 310053
- Keywords:
Neuralgia;
Anxiety-like behavior;
Peripheral monocyte;
Hippocampal CA3 area;
Immunofluorescence;
Mouse
- From:
Acta Anatomica Sinica
2024;55(6):667-676
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the infiltration of peripheral monocyte in the hippocampal CA3 area in neuralgia mice at different time points and explore the effects of the infiltration on neuralgia and the neuralgia-induced anxiety-like behavior in mice.Methods The healthy male C57 mice were randomly divided into four groups:sham,sciatic nerve branch selective injury(SNI)model(SNI),CCR2 inhibitor RS102895(SNI+RS102895)and microglial inhibitor minocycline(MC)(SNI+MC)groups.Both the sham and SNI groups were further divided into 7 days,14 days and 18 days groups,and the SNI+RS102895 and SNI+MC groups were sampled on the 18th day.Neuralgia was induced by SNI,and mechanical hyperalgesia was assessed by paw withdrawal threshold(PWTs)at different time points.Elevated plus maze(EPM)and open field test(OFT)were performed respectively two days and one day before sacrifice.Immunofluorescence was used to observe the expressions of leukocyte differentiation antigen 45(CD45)and the co-expression with microglial markers ionized calcium binding adaptor molecule-1(IBA-1),transmembrane protein 119(TMEM119),astrocyte marker glial fibrillary acidic protein(GFAP),and neuronal marker neuronal nuclei(NeuN)in the hippocampal CA3.The percentage of monocytes in the whole brain of 14 days SNI mice was determined by flow cytometry.Minocycline at 90 mg/(kg·d),RS 102895 at 5 mg/(kg·d)and saline were administered orally on the 5th to 16th day in the corresponding 18 days groups,and the effects of blocking monocyte infiltration on neuralgia and anxiety-like behavior and the expressions of CD45 and 1BA-1 in CA3 region of hippocampus were observed.Results On the first day after SNI,the PWTs of mice in the 7 days and 14 days groups decreased and continued until before sacrifice(P<0.01).The CD45 expression did little in the 7 days sham group.Compared with the sham group at the same time point,the CD45 expression did not increase in 7 days SNI mice((P>0.05)and increased significantly in 14 days SNI mice(P<0.01),only slightly co-expressed with IBA-1 and TMEM119 and no co-expression with GFAP and NeuN,the percentage of monocytes in the whole brain increased significantly in 14 days SNI mice(P<0.01).Inhibition of microglial activation or CCR2 expression reduced the expression of CD45 in the CA3 in SNI mice(P<0.01),increased the PWTs(P<0.01)and alleviated anxiety-like behavior in SNI mice(P<0.01).Conclusion There was an infiltration of peripheral monocytes in the hippocampal CA3 region after 14 days of SNI-induced neuralgia,which might be involved in the maintenance of neuralgia and the development of neuralgia-induced anxiety-like behaviors.