Dataset Information

SiNiSan Ameliorates the Depression-Like Behavior of Rats That Experienced Maternal Separation Through 5-HT1A Receptor/CREB/BDNF Pathway.

ABSTRACT: Background: Early adverse life stress is an important dangerous factor in the development of psychiatric disorders, particularly depression. Available clinical antidepressant agents, such as fluoxetine, [a selective serotonin reuptake inhibitor (SSRI)], are unsatisfactory because of their side effects. SiNiSan (SNS) is a classic Chinese medicine prescription regarded to disperse stagnated liver qi to relieve qi stagnation. Therefore, this study was designed to detect the effects and molecular mechanism of SNS treatment in rats subjected to maternal separation (MS). Method: Male neonatal Wistar rats were divided into six groups including control + ddH₂O, MS + ddH₂O, MS + fluoxetine (5 g/kg), MS + SNS -low dose (2.5 g/kg), MS + SNS -medium dose (5 g/kg), MS + SNS -high dose (10 g/kg). The volume of drugs and ddH2O in each group are according to the weight of rats every day (10 mL/kg). Each group comprised 16 pups with 8 young and 8 adult pups. Except for the control group, all MS groups were separated from their mothers for 4 h/day from 9:00 to 13:00 during postnatal days (PNDs) 1 to 21. After MS, the six groups were intragastrically administered with ddH2O, fluoxetine, and different doses of SNS until PND 28 (for young pups) and PND 56 (for adult pups). The pups were weighed every day, and depression-like behavior was assessed by sucrose preference test, open field test, and forced swimming test. Serotonin 1A (5-HT1A) receptor, phosphorylated protein kinase A (p-PKA) substrate, cAMP response element-binding protein (CREB), p-CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were examined by Western blot, and in situ 5-HT1A receptor expression was measured by IHC. Results: Young and adult MS rats exhibited depression-like behavior. However, the depression-like behavior was ameliorated by SNS in both age groups. The levels of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus were reduced in young and adult MS rats. SNS treatment significantly up-regulated the expression of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus of adult MS rats. However, few significant effects on the protein expression were observed in the young MS rats. Conclusion: MS in infancy could develop depression-like behavior in young and adult. SNS treatment may perform antidepressant effects on young and adult MS rats through the BDNF/PKA/CREB pathway.

SUBMITTER: Cao K

PROVIDER: S-EPMC6447714 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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SiNiSan Ameliorates the Depression-Like Behavior of Rats That Experienced Maternal Separation Through 5-HT1A Receptor/CREB/BDNF Pathway.

Cao Kerun K Shen Chongkun C Yuan Yumei Y Bai Shasha S Yang Lei L Guo Lili L Zhang Rong R Shi Yafei Y

Frontiers in psychiatry 20190328

<b>Background:</b> Early adverse life stress is an important dangerous factor in the development of psychiatric disorders, particularly depression. Available clinical antidepressant agents, such as fluoxetine, [a selective serotonin reuptake inhibitor (SSRI)], are unsatisfactory because of their side effects. SiNiSan (SNS) is a classic Chinese medicine prescription regarded to disperse stagnated liver qi to relieve qi stagnation. Therefore, this study was designed to detect the effects and molec ...[more]

PMID: 30984042

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Project description:Objective: To investigate the mechanisms depression-related manifestations ameliorated by electroacupuncture on genome-wide transcriptomes of the frontal cortex at the molecular level, we evaluated unbiased genome-wide RNA sequencing of depression-related rats suffer from maternal separation (MS). Methods: Rats were randomly divided into control, MS, electro-acupuncture treatment(EA) group . We demonstrated depression-like behavior deficiencies in a sucrose preference test and a forced swimming test in a rat model with neonatal maternal separation. Repeated EA treatment at the acupoints Baihui (GV20) and Yintang (GV29) during the adult period was shown to be remarkably attenuated above behavioral deficits. Sequencing was performed using Hiseq Xten (Illumina, USA). Results: Based on the data from RNA-seq analysis, for mRNA, 48 genes were significantly and differentially expressed in MS rats relative to control rats, with 39 up-regulated genes and 9 down-regulated genes. 40 genes in the EA rats relative to the MS rats show differential expression, with 21 genes up-regulated and 18 genes down-regulated. For lncRNA, 11 genes increased significantly in the MS rats relative and 4 genes decreased relative to controls. 31 genes increased in the EA rats relative to the MS rats while 1 gene decreased. For circRNA, 20 genes increased significantly in the MS rats relative to control rats and 17 genes decreased. 18 genes increased in the EA rats relative to the MS rats while 28 genes decreased. Using ceRNA, we narrowed the targets of mRNA from 31 to 17 genes with a circRNA_miRNA_mRNA network, and narrowed the targets of mRNA from 31 to 8 genes with an lncRNA_miRNA_mRNA network, pointing the way for further studies to verify the genes and describe their function. Conclusions: Our investigation demonstrates the first analysis of the frontal cortex genome-wide transcriptomes in depression rats under maternal separation by RNA-seq technology. These results suggest that EA at GV20 and GV29 ameliorates depression-related manifestations by regulating the expression of multiple genes.

Project description:Background and purpose: Astrocyte-mediated neuroinflammation plays an important role in anesthetic isoflurane-induced cognitive impairment. Roflumilast, a selective inhibitor of phosphodiesterase-4 (PDE-4) used for the treatment of chronic obstructive pulmonary disease (COPD), has displayed a wide range of anti-inflammatory capacity in different types of cells and tissues. In the current study, we aimed to investigate whether roflumilast possesses a protective effect against isoflurane-induced insults in mouse primary astrocytes. Methods: Primary astrocytes were isolated from the cerebral cortices of immature rats. The production of NO was determined using DAF-FM DA staining assay. QRT-PCR and western blot were used to evaluate the expression levels of iNOS, COX-2, and BDNF in the astrocytes treated with different therapies. The gene expressions and concentrations of IL-6 and MCP-1 released by the astrocytes were detected using qRT-PCR and ELISA, respectively. The expression levels of phosphorylated CREB and PGE2 were determined using western blot and ELISA, respectively. H89 was introduced to evaluate the function of CREB. Recombinant human BDNF and ANA-12 were used to verify the role of BDNF. Results: The upregulated iNOS, excessive production of NO, IL-6, and MCP-1, and activated COX-2/PGE2 signaling pathways in the astrocytes induced by isoflurane were significantly reversed by the introduction of roflumilast, in a dose-dependent manner. Subsequently, we found that BDNF could be upregulated by roflumilast, which was verified to be related to the activation of CREB and blocked by H89 (a CREB inhibitor). In addition, the COX-2/PGE2 signaling pathway activated by isoflurane can be inactivated by recombinant human BDNF. Finally, the regulatory effect of roflumilast against the isoflurane-activated COX-2/PGE2 signaling pathway was significantly blocked by ANA-12, which is a BDNF inhibitor. Conclusion: Roflumilast might ameliorate isoflurane-induced inflammation in astrocytes via the CREB/BDNF signaling pathway.

Dataset Information

SiNiSan Ameliorates the Depression-Like Behavior of Rats That Experienced Maternal Separation Through 5-HT1A Receptor/CREB/BDNF Pathway.

Publications

SiNiSan Ameliorates the Depression-Like Behavior of Rats That Experienced Maternal Separation Through 5-HT1A Receptor/CREB/BDNF Pathway.

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