Effects of ganglioside GM1 and neural growth factor on neural stem cell proliferation and differentiation

Abstract

ABSTRACT. Neurogenesis, recovery from nerve injury, neurodegeneration, and Parkinson's disease affect people's health, yet the underlying molecular mechanisms remain elusive. Here, we investigated the effect of ganglioside GM1 and neural growth factor (NGF) on neural stem cell (NSC) proliferation and differentiation in vitro to provide a scientific basis for comprehensive treatment of nervous system diseases via NSC application. As widely applied methods of relatively high accuracy, cell counts and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays were used to assess NSC proliferation. In addition, western blotting 2 Q. Wang et al. Genetics and Molecular Research 15 (3): gmr.15038376 was employed to determine NSC differentiation. Cell counts and MTT assays demonstrated that in epidermal growth factor (EGF)-and basic fibroblast growth factor (bFGF)-containing medium, a high concentration of GM1, but not NGF, significantly elevated NSC proliferation. In NSC cultures lacking EGF and bFGF, cell counts and MTT values were significantly increased compared to those in the negative control group on days 4, 7, and 10 after GM1 (25, 100, and 200 ng/mL) but not NGF (25, 50, 100, and 200 ng/mL) treatment. Western blotting revealed significantly increased expression of nestin (an NSC marker) in NSCs treated with GM1, and upregulation of glial fibrillary acidic protein (a glial cell marker) and neuron-specific enolase (a neuron marker) in those administered NGF. Our results suggest that GM1 and NGF induce NSC proliferation and differentiation, respectively, in a dose-dependent manner.

The crosstalk between glycosphingolipids and neural stem cells

“…The dose-dependent effects of GM1 and GD3, for instance, are most intriguing (Itokazu et al 2013;Wang et al 2016). It is already known that NSCs express GD3 as the most abundant ganglioside (Nakatani et al 2010), and co-localize with EGFR regulating cell proliferation (Itokazu et al 2013) (Fig.…”

“…; Wang et al . ). EGFR interaction with the N‐linked GlcNAc oligosaccharides portion of GM3 (NeuAcα2‐3Galβ1‐4Glcβ1‐1′Cer), in a cis fashion (Regina Todeschini and Hakomori ), which has a negative impact on the EGFR tyrosine kinase (Hanai et al .…”

“…These phenomena were accompanied by a switch, in the GD3S-KO NSCs, of EGFR that was found mainly in the high-density layers (Wang and Yu 2013). It was found that GD3 is necessary for the long-term preservation of NSC populations in the postnatal mouse brain (Wang et al 2014) and that GM1 and GD3 at low concentrations (from 0.001 to 10 lM) are important factors for NSCs proliferation, whereas higher concentrations (50 and 200 lM) induced a reduction in proliferation (Itokazu et al 2013;Wang et al 2016). EGFR interaction with the N-linked GlcNAc oligosaccharides portion of GM3 (NeuAca2-3Galb1-4Glcb1-1 0 Cer), in a cis fashion (Regina Todeschini and Hakomori 2008), which has a negative impact on the EGFR tyrosine kinase (Hanai et al 1988), was first reported in Hakomori's laboratory.…”

Curative effects of GM1 in the treatment of severe ischemic brain injury and its effects on serum TNF-α and NDS

“…Over the past few years, it was found that the neuroprotective drug monosialotetrahexosyl ganglioside (GM1) promotes growth and repair the neurological impairment. As reported, the exogenous GM1 has been used to promote the nervous system cell regeneration and synapse formation ( 7 , 8 ). However, the role of GM1 in patients with severe ischemic brain injury is rarely reported.…”

The CLIMB (Complex Lipids In Mothers and Babies) study: protocol for a multicentre, three-group, parallel randomised controlled trial to investigate the effect of supplementation of complex lipids in pregnancy, on maternal ganglioside status and subsequent cognitive outcomes in the offspring

“…1 2 Previous reviews confirm an essential role of GA in brain structure and function. [3][4][5] They are also reported to provide protection from inflammation, neurodegeneration, 6 7 apoptosis and tumours, 8 9 to accelerate neural development of the newborn [10][11][12][13] and to contribute to learning and memory. [14][15][16] In addition, decreased levels of GA contribute to The CLIMB (Complex Lipids In Mothers and Babies) study: protocol for a multicentre, three-group, parallel randomised controlled trial to investigate the effect of supplementation of complex lipids in pregnancy, on maternal ganglioside status and subsequent cognitive outcomes in the offspring Shuai Huang, 1,2 Ting-Ting Mo, 3 Tom Norris, 4 Si Sun, 3 Ting Zhang, 1,2 Ting-Li Han, 2,5 Angela Rowan, 6 Yin-Yin Xia, 3 Hua Zhang, 1,2 Hong-Bo Qi, 1,2 Philip N Baker 2,5,7 Mothers and Babies) study is the first large clinical trial to perform interventions with complex milk lipids (CML) during pregnancy in humans.…”