Ginsenoside Rg1 Prevents Chemotherapy-Induced Cognitive Impairment: Associations with Microglia-Mediated Cytokines, Neuroinflammation, and Neuroplasticity.

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  • Additional Information
    • Source:
      Publisher: Humana Press Country of Publication: United States NLM ID: 8900963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1182 (Electronic) Linking ISSN: 08937648 NLM ISO Abbreviation: Mol Neurobiol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Clifton, NJ : Humana Press, c1987-
    • Subject Terms:
      Neuronal Plasticity*/drug effects; Antineoplastic Agents/*adverse effects ; Brain/*pathology ; Cognitive Dysfunction/*prevention & control ; Cytokines/*metabolism ; Ginsenosides/*therapeutic use ; Inflammation/*drug therapy ; Microglia/*pathology; Animals ; Anxiety/complications ; Anxiety/physiopathology ; Behavior, Animal ; Biomarkers/blood ; Brain/drug effects ; Brain/physiopathology ; Cognition/drug effects ; Cognitive Dysfunction/chemically induced ; Cognitive Dysfunction/drug therapy ; Cognitive Dysfunction/physiopathology ; Cytokines/blood ; Dendritic Spines/drug effects ; Dendritic Spines/pathology ; Female ; Ginsenosides/pharmacology ; Glial Fibrillary Acidic Protein/metabolism ; Inflammation/blood ; Inflammation/complications ; Inflammation/pathology ; Locomotion/drug effects ; Magnetic Resonance Imaging ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia/drug effects ; PC12 Cells ; Rats
    • Abstract:
      Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether ginsenoside Rg1, a ginseng-derived compound, could prevent chemobrain and its underlying mechanisms. A mouse model of chemobrain was developed with three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination at a 2-day interval. Rg1 (5 and 10 mg/kg daily) was given 1 week prior to DAC regimen for 3 weeks. An amount of 10 mg/kg Rg1 significantly improved chemobrain-like behavior in water maze test. In vivo neuroimaging revealed that Rg1 co-treatment reversed DAC-induced decreases in prefrontal and hippocampal neuronal activity and ameliorated cortical neuronal dendritic spine elimination. It normalized DAC-caused abnormalities in the expression of multiple neuroplasticity biomarkers in the two brain regions. Rg1 suppressed DAC-induced elevation of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but increased levels of the anti-inflammatory cytokines IL-4 and IL-10 in multiple sera and brain tissues. Rg1 also modulated cytokine mediators and inhibited DAC-induced microglial polarization from M2 to M1 phenotypes. In in vitro experiments, while impaired viability of PC12 neuroblastic cells and hyperactivation of BV-2 microglial cells, a model of neuroinflammation, were observed in the presence of DAC, Rg1 co-treatment strikingly reduced DAC's neurotoxic effects and neuroinflammatory response. These results indicate that Rg1 exerts its anti-chemobrain effect in an association with the inhibition of neuroinflammation by modulating microglia-mediated cytokines and the related upstream mediators, protecting neuronal activity and promoting neuroplasticity in particular brain regions associated with cognition processing.
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    • Grant Information:
      17115017 General Research Fund
    • Contributed Indexing:
      Keywords: Chemobrain; Cytokines; Ginsenoside Rg1; In vivo neuroimaging; Neuroinflammation; Neuroplasticity
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Biomarkers)
      0 (Cytokines)
      0 (Ginsenosides)
      0 (Glial Fibrillary Acidic Protein)
      PJ788634QY (ginsenoside Rg1)
    • Publication Date:
      Date Created: 20190120 Date Completed: 20191217 Latest Revision: 20200225
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s12035-019-1474-9
    • Accession Number:
      30659419