Mechanism of Chaijin Jieyu Anshen Formula in regulating synaptic damage in nucleus accumbens neurons of rats with insomnia complicated with depression through TREM2/C1q axis.
10.19540/j.cnki.cjcmm.20250509.403
- Author:
Ying-Juan TANG
1
;
Jia-Cheng DAI
1
;
Song YANG
1
;
Xiao-Shi YU
1
;
Yao ZHANG
1
;
Hai-Long SU
1
;
Zhi-Yuan LIU
1
;
Zi-Xuan XIANG
1
;
Jun-Cheng LIU
2
;
Hai-Xia HE
3
;
Jian LIU
3
;
Yuan-Shan HAN
3
;
Yu-Hong WANG
4
;
Man-Shu ZOU
4
Author Information
1. Technology Innovation Center, Hunan University of Chinese Medicine Changsha 410208, China.
2. Pengzhou Hospital of Traditional Chinese Medicine Chengdu 611930, China.
3. the First Hospital of Hunan University of Chinese Medicine Changsha 410007, China Hunan Provincial Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Depressive Diseases Changsha 410208, China.
4. Technology Innovation Center, Hunan University of Chinese Medicine Changsha 410208, China Hunan Provincial Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Depressive Diseases Changsha 410208, China.
- Publication Type:Journal Article
- Keywords:
Chaijin Jieyu Anshen Formula;
complement protein C1q;
insomnia complicated with depression;
triggering receptor expressed on myeloid cells 2(TREM2)
- MeSH:
Animals;
Male;
Rats;
Nucleus Accumbens/metabolism*;
Drugs, Chinese Herbal/administration & dosage*;
Depression/complications*;
Membrane Glycoproteins/genetics*;
Rats, Sprague-Dawley;
Sleep Initiation and Maintenance Disorders/complications*;
Neurons/metabolism*;
Receptors, Immunologic/genetics*;
Signal Transduction/drug effects*;
Synapses/metabolism*
- From:
China Journal of Chinese Materia Medica
2025;50(16):4538-4545
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
