Skip to main content
SpringerLink
Log in

Ginsenoside Rd maintains adult neural stem cell proliferation during lead-impaired neurogenesis

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Lead exposure attracts a great deal of public attention due to its harmful effects on human health. Even low-level lead (Pb) exposure reduces the capacity for neurogenesis. It is well known that microglia-mediated neurotoxicity can impair neurogenesis. Despite this, few in vivo studies have been conducted to understand the relationship between acute Pb exposure and microglial activation. We investigated whether the acute Pb exposure altered the expression of a marker of activated microglial cells (Iba-1), and markers of neurogenesis (BrdU and doublecortin) in aging rats. As compared to controls, Pb exposure significantly enhanced the expression of Iba-1 immunoreactivity; increased the expression levels of IL-1β, IL-6, and TNF-α and decreased the numbers of BrdU+ and doublecortin+ cells. Our prior work demonstrated that ginsenoside Rd (Rd), one of the major active ingredients in Panax ginseng, was neuroprotective in a variety of paradigms involving anti-inflammatory mechanisms. Thus, we further examined whether Rd could attenuate Pb-induced phenotypes. Compared with the Pb exposure group, Rd pretreatment indeed attenuated the effects of Pb exposure. These results suggest that Rd may be neuroprotective in old rats following acute Pb exposure, which involves limitation of microglial activation and maintenance of NSC proliferation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Brodkin E, Copes R, Mattman A et al (2007) Lead and mercury exposures: interpretation and action. CMAJ 176:59–63

    PubMed  Google Scholar 

  2. Canfield RL, Henderson CR Jr, Cory-Slechta DA et al (2003) Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med 348:1517–1526

    Article  PubMed  CAS  Google Scholar 

  3. Min MO, Singer LT, Kirchner HL et al (2009) Cognitive development and low-level lead exposure in poly-drug exposed children. Neurotoxicol Teratol 31:225–231

    Article  PubMed  CAS  Google Scholar 

  4. Jiang YM, Long LL, Zhu XY et al (2008) Evidence for altered hippocampal volume and brain metabolites in workers occupationally exposed to lead: a study by magnetic resonance imaging and (1)H magnetic resonance spectroscopy. Toxicol Lett 181:118–125

    Article  PubMed  CAS  Google Scholar 

  5. Stewart WF, Schwartz BS, Davatzikos C et al (2006) Past adult lead exposure is linked to neurodegeneration measured by brain MRI. Neurology 66:1476–1484

    Article  PubMed  CAS  Google Scholar 

  6. Schwartz BS, Stewart WF, Bolla KI et al (2000) Past adult lead exposure is associated with longitudinal decline in cognitive function. Neurology 55:1144–1150

    Article  PubMed  CAS  Google Scholar 

  7. White LD, Cory-Slechta DA, Gilbert ME et al (2007) New and evolving concepts in the neurotoxicology of lead. Toxicol Appl Pharmacol 225:1–27

    Article  PubMed  CAS  Google Scholar 

  8. Struzynska L (2009) A glutamatergic component of lead toxicity in adult brain: the role of astrocytic glutamate transporters. Neurochem Int 55(1–3):151–156

    Article  PubMed  CAS  Google Scholar 

  9. Neal AP, Stansfield KH, Worley PF et al (2010) Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release: potential role of NMDA receptor-dependent BDNF signaling. Toxicol Sci 116:249–263

    Article  PubMed  CAS  Google Scholar 

  10. Toscano CD, Hashemzadeh-Gargari H, McGlothan JL et al (2002) Developmental Pb2 + exposure alters NMDAR subtypes and reduces CREB phosphorylation in the rat brain. Brain Res Dev Brain Res 139(2):217–226

    Article  PubMed  CAS  Google Scholar 

  11. Struzynska L (2009) A glutamatergic component of lead toxicity in adult brain: the role of astrocytic glutamate transporters. Neurochem Int 55:151–156

    Article  PubMed  CAS  Google Scholar 

  12. Jaako-Movits K, Zharkovsky T, Romantchik O et al (2005) Developmental lead exposure impairs contextual fear conditioning and reduces adult hippocampal neurogenesis in the rat brain. Int J Dev Neurosci 23:627–635

    Article  PubMed  CAS  Google Scholar 

  13. Verina T, Rohde CA, Guilarte TR (2007) Environmental lead exposure during early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats. Neuroscience 145:1037–1047

    Article  PubMed  CAS  Google Scholar 

  14. Yang XL, Guo TK, Wang YH et al (2012) Ginsenoside Rd attenuates the inflammatory response via modulating p38 and JNK signaling pathways in rats with TNBS-induced relapsing colitis. Int Immunopharmacol 12:408–414

    Article  PubMed  CAS  Google Scholar 

  15. Yang F, Wang JC, Han JL et al (2008) Different effects of mild and severe seizures on hippocampal neurogenesis in adult rats. Hippocampus 18:460–468

    Article  PubMed  Google Scholar 

  16. Hamidinia SA, Erdahl WL, Chapman CJ et al (2006) Monensin improves the effectiveness of meso-dimercaptosuccinate when used to treat lead intoxication in rats. Environ Health Perspect 114:484–493

    Article  PubMed  CAS  Google Scholar 

  17. Stangle DE, Strawderman MS, Smith D et al (2004) Reductions in blood lead overestimate reductions in brain lead following repeated succimer regimens in a rodent model of childhood lead exposure. Environ Health Perspect 112:302–308

    Article  PubMed  CAS  Google Scholar 

  18. Liu X, Wang L, Wen A et al (2012) Ginsenoside-Rd improves outcome of acute ischaemic stroke—a randomized, double-blind, placebo-controlled, multicenter trial. Eur J Neurol doi. doi:10.1111/j.1468-1331.2011.03634.x

    Google Scholar 

  19. Zhang C, Du F, Shi M et al (2012) Ginsenoside Rd Protects Neurons Against Glutamate-Induced Excitotoxicity by Inhibiting Ca(2 +) Influx. Cell Mol Neurobiol 32:121–128

    Article  PubMed  CAS  Google Scholar 

  20. Ye R, Li N, Han J et al (2009) Neuroprotective effects of ginsenoside Rd against oxygen-glucose deprivation in cultured hippocampal neurons. Neurosci Res 64:306–310

    Article  PubMed  CAS  Google Scholar 

  21. Ye R, Zhang X, Kong X et al (2011) Ginsenoside Rd attenuates mitochondrial dysfunction and sequential apoptosis after transient focal ischemia. Neuroscience 178:169–180

    Article  PubMed  CAS  Google Scholar 

  22. Ye R, Kong X, Yang Q et al (2011) Ginsenoside Rd attenuates redox imbalance and improves stroke outcome after focal cerebral ischemia in aged mice. Neuropharmacology 61:815–824

    Article  PubMed  CAS  Google Scholar 

  23. Ye R, Yang Q, Kong X et al (2011) Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory response after transient focal ischemia in rats. Neurochem Int 58:391–398

    Article  PubMed  CAS  Google Scholar 

  24. Zhang Y, Zhou L, Zhang X et al (2012) Ginsenoside-Rd attenuates TRPM7 and ASIC1a but promotes ASIC2a expression in rats after focal cerebral ischemia. Neurol Sci 33(5):1125–1131

    Article  PubMed  CAS  Google Scholar 

  25. Zheng W, Perry DF, Nelson DL, Aposhian HV (1991) Protection of cerebrospinal fluid against toxic metals by the choroid plexus. FASEB J. 5:2188–2193

    PubMed  CAS  Google Scholar 

  26. Abrous DN, Koehl M, Le Moal M (2005) Adult neurogenesis: from precursors to network and physiology. Physiol Rev 85:523–569

    Article  PubMed  CAS  Google Scholar 

  27. Kuzumaki N, Ikegami D, Tamura R et al (2010) Hippocampal epigenetic modification at the doublecortin gene is involved in the impairment of neurogenesis with aging. Synapse 64:611–616

    Article  PubMed  CAS  Google Scholar 

  28. Davidovics Z, DiCicco-Bloom E (2005) Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture. J Neurosci Res 80:817–825

    Article  PubMed  CAS  Google Scholar 

  29. Gleeson JG, Lin PT, Flanagan LA et al (1999) Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23:257–271

    Article  PubMed  CAS  Google Scholar 

  30. Huang F, Schneider JS (2004) Effects of lead exposure on proliferation and differentiation of neural stem cells derived from different regions of embryonic rat brain. Neurotoxicology 25:1001–1012

    Article  PubMed  CAS  Google Scholar 

  31. Curtis MA, Faull RL, Eriksson PS (2007) The effect of neurodegenerative diseases on the subventricular zone. Nat Rev Neurosci 8:712–723

    Article  PubMed  CAS  Google Scholar 

  32. Graham DL, Grace CE, Braun AA et al (2011) Effects of developmental stress and lead (Pb) on corticosterone after chronic and acute stress, brain monoamines, and blood Pb levels in rats. Int J Dev Neurosci 29:45–55

    Article  PubMed  CAS  Google Scholar 

  33. Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302:1760–1765

    Article  PubMed  CAS  Google Scholar 

  34. Cacci E, Claasen JH, Kokaia Z (2005) Microglia-derived tumor necrosis factor-alpha exaggerates death of newborn hippocampal progenitor cells in vitro. J Neurosci Res 80:789–797

    Article  PubMed  CAS  Google Scholar 

  35. Liu YP, Lin HI, Tzeng SF (2005) Tumor necrosis factor-alpha and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture. Brain Res 1054:152–158

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Prof. Wen Jiang for his insightful comments and Ms. Dongyun Feng for technical support. This study was supported by grants from the National Natural Science Foundation of China (Grant Nos. 31170801, 81070950 and 81171236).

Author information

Authors and Affiliations

  1. Department of Neurology, Xijing Hospital, The Fourth Military Medical University, No.169, West Changle Road, Xi’an, 710032, China

    Bing Wang, Guodong Feng, Yunxia Zhang, Ming Shi & Gang Zhao

  2. Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, China

    Jing Ma

  3. The 538 hospital of PLA, Han Zhong, China

    Bing Wang

  4. Department of Biomedical Engineering, Fourth Military Medical University, Xi’an, China

    Chi Tang

  5. The 421 hospital of PLA, Guangzhou, China

    Li Wang

  6. Lin tong Air Force Aeromedical Training Institute, Xi’an, China

    Haoran Cheng

Authors
  1. Bing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guodong Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chi Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haoran Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yunxia Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jing Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ming Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ming Shi or Gang Zhao.

Additional information

Bing Wang, Guodong Feng, Chi Tang, and Li Wang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, B., Feng, G., Tang, C. et al. Ginsenoside Rd maintains adult neural stem cell proliferation during lead-impaired neurogenesis. Neurol Sci 34, 1181–1188 (2013). https://doi.org/10.1007/s10072-012-1215-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-012-1215-6

Keywords

Search

Navigation