Dysregulation of Neuregulin-1/ErbB signaling in the hippocampus of rats after administration of doxorubicin

Liao, Dehua; Guo, Yujin; Xiang, Da‐Xiong; Dang, Ruili; Xu, Pengfei; Cai, Hualin; Cao, Lizhi; Jiang, Pei

doi:10.2147/dddt.s151511

Cited by 19 publications

(9 citation statements)

References 33 publications

(36 reference statements)

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“…The results from the present study also indicated that DOX suppressed activation of the downstream Akt and Erk pathway, which was detected by the phosphorylation of its mediators Erk and Akt, respectively. This result was in accordance with previous findings (32). Hang et al (11) also demonstrated that BDNF/TrkB signaling is necessary in preventing cardiotoxicity following administration of DOX.…”

Section: Discussionsupporting

confidence: 93%

Involvement of neurotrophic signaling in doxorubicin‑induced cardiotoxicity

Liao

Zhang

et al. 2019

Exp Ther Med

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Dose dependent cardiotoxicity is the primary side effect of doxorubicin (DOX), but the underlying molecular mechanisms remain unclear. An increasing amount of evidence has demonstrated that neurotrophic signaling plays a pivotal role in both neurons and the heart, but the biological association between neurotrophic signaling and DOX-induced cardiotoxicity remains unknown. The present study determined the level of neurotrophins and their receptors in the heart of rats following DOX administration. DOX was administered 7 times at a dose of 2.5 mg/kg once every 2 days via intraperitoneal injection. The present study revealed that cardiac injury parameters, such as creatine kinase (CK), creatine kinase-myocardial bound, lactate dehydrogenase, troponin T and aspartate transaminase in serum were significantly increased in the DOX group. Both the gene and protein expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the heart were markedly decreased following DOX treatment. Notably, the protein level of BDNF in the serum was inhibited in DOX-treated rats, whereas DOX induced a significant increase in the protein level of NGF in the serum. DOX induced a significant decrease in the level of tropomyosin-associated kinase A (TrkA) and the ratio of pTrkA/TrkA and pTrkB/TrkB. Furthermore, the administration of DOX suppressed downstream protein kinase B and extracellular signal regulated kinase phosphorylation. The present study first demonstrated that BDNF/TrkB signaling and NGF/TrkA signaling were altered by DOX, which indicated that neurotrophic signaling was involved in DOX-induced cardiotoxicity.

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Section: Discussionsupporting

confidence: 93%

Involvement of neurotrophic signaling in doxorubicin‑induced cardiotoxicity

Liao

Zhang

et al. 2019

Exp Ther Med

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“…The novelty-suppressed feeding test (NSFT) was adapted from previous study [15]. Before testing, rats were fasted for 24 h. The rats were placed in an open field (75 × 75 × 40 cm).…”

Section: Behavioral Testsmentioning

confidence: 99%

Antidepressant activity of ω-3 polyunsaturated fatty acids in ovariectomized rats: role of neuroinflammation and microglial polarization

Song

Zhang

et al. 2020

Lipids Health Dis

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Background: Menopause predisposes individuals to affective disorders, such as depression, which is tightly related to neuroinflammation. While the neuroinflammatory condition has been demonstrated in ovariectomized (OVX) rodents, there is limited evidence concerning microglial polarization, a key process in brain immune activation, in menopause-related brain. Methods: Therefore, the present study aims to evaluate the polarized microglia in long-term OVX rats and we further explored whether supplementation of ω-3 polyunsaturated fatty acids (PUFA), the pleiotropic bioactive nutrient, is effective in the neurobehavioral changes caused by OVX. Results: Our data showed that OVX-induced anxiety and depression-like behaviors in rats, accompanied with increased neural apoptosis and microglial activation in the hippocampus. Additionally, OVX enhanced proinflammatory cytokines expression and suppressed the expression of anti-inflammatory cytokine, IL-10. Correspondingly, OVX reinforced NFκB signaling and shifted the microglia from immunoregulatory M2 phenotype to proinflammatory M1 phenotype. Meanwhile, daily supplementation with PUFA suppressed microglial M1 polarization and potentiated M2 polarization in OVX rats. In parallel, PUFA also exerted antidepressant and neuroprotective activities, accompanied with neuroimmune-modulating actions. Conclusion: Collectively, the present study firstly demonstrated the disturbed microglial polarization in the OVX brain and provide novel evidence showing the association between the antidepressant actions of PUFA and the restraint neuroinflammatory progression.

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“…Oxytocin improved depression symptom by down-regulating c-fos protein and by inhibiting the ERK pathway as well [66]. (4) The ErbB pathway was also associated with depression by adjusting neuregulin and affecting downstream Akt and ERK signaling pathways [67,68]. EGF and VEGF were parts of the ErbB family and were associated with nerve growth and nutrition [69].…”

Section: Discussionmentioning

confidence: 99%

Identification of the significant pathways of Banxia Houpu decoction in the treatment of depression based on network pharmacology

et al. 2020

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Banxia Houpu decoction (BXHPD) has been used to treat depression in clinical practice for centuries. However, the pharmacological mechanisms of BXHPD still remain unclear. Network Pharmacology (NP) approach was used to explore the potential molecular mechanisms of BXHPD in treating depression. Potential active compounds of BXHPD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database. STRING database was used to build a interaction network between the active compounds and target genes associated with depression. The topological features of nodes were visualized and calculated. Significant pathways and biological functions were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 44 active compounds were obtained from BXHPD, and 121 potential target genes were considered to be therapeutically relevant. Pathway analysis indicated that MAPK signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway and PI3K-Akt pathway were significant pathways in depression. They were mainly involved in promoting nerve growth and nutrition and alleviating neuroinflammatory conditions. The result provided some potential ways for modern medicine in the treatment of depression.

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Dysregulation of Neuregulin-1/ErbB signaling in the hippocampus of rats after administration of doxorubicin

Cited by 19 publications

References 33 publications

Involvement of neurotrophic signaling in doxorubicin‑induced cardiotoxicity

Involvement of neurotrophic signaling in doxorubicin‑induced cardiotoxicity

Antidepressant activity of ω-3 polyunsaturated fatty acids in ovariectomized rats: role of neuroinflammation and microglial polarization

Identification of the significant pathways of Banxia Houpu decoction in the treatment of depression based on network pharmacology

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