GM1 and NGF modulate Ca²⁺homeostasis and GAP43 mRNA expression in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate

Abstract

Monosialoganglioside (GM1) has been considered to have a neurotrophic factor-like activity. Nerve growth factor (NGF), a member of the neurotrophin family, is essential for neuronal survival, differentiation and maturation. The aim of the present study was to investigate whether co-administration of GM1 and NGF reverses glutamate (Glu) neurotoxicity in primary cultured rat embryonic dorsal root ganglion (DRG) neurons. DRG neurons were exposed to Glu (2 mmol/1), Glu (2 mmol/1) plus GM1 (10 microg/ml), Glu (2 mmol/l) plus NGF (10 ng/ml), Glu (2 mmol/l) plus GM1 (5 microg/ml) and NGF (5 ng/ml) and then processed for detecting intracellular concentrations of Ca2+ ([Ca2+] i) by confocal laser scanning microscopy and growth-associated protein 43 (GAP43) mRNA by RT-PCR. The fluorescent intensity in Glu plus GM1 and NGF incubated neurons was the lowest as compared with that in other groups. The expression of GAP43 mRNA in Glu plus GM1 and NGF incubated neurons was the highest as compared with that in other groups. These results implicated that GM1 and NGF have synergistic neuroprotective effects on DRG neurons with excitotoxicity induced by Glu in vitro.

Activation of ERK1/2 and PI3K/Akt by IGF-1 on GAP-43 Expression in DRG Neurons with Excitotoxicity Induced by Glutamate In Vitro

“…GAP-43 expression increased in the injured nerve and in the corresponding DRG after peripheral nerve injury (Kato et al 2010). The expression of GAP-43 in cultured DRG neurons was affected by different drugs or factors, such as a nucleoside reverse transcriptase inhibitor 2 0 ,3 0 -dideoxycytidine (zalcitabine), an immunophilin ligand FK506 (Keswani et al 2004), brain-derived neurotrophic factor (BDNF) (Gupta et al 2009), monosialoganglioside and nerve growth factor (Huang et al 2007). Interestingly, GAP-43 is an important mediator of the neurotrophic effects of S18986 (a positive AMPA receptor modulator) and BDNF on neuronal survival and plasticity (Gupta et al 2009).…”

“…influx (Sanelli et al 2007). There is now convincing evidence that excessive accumulation of the excitatory amino acid Glu in the extracellular space is toxic to central mammalian neurons (Michaels and Rothman 1990) and peripheral neurons (Huang et al 2007). The presence of IGF-1 is required to depress the rise in intracellular Ca 2?…”

Co-administration of Monosialoganglioside and Skeletal Muscle Cells on Dorsal Root Ganglion Neuronal Phenotypes In Vitro

“…GM1 ganglioside is protective against various neurological insults, including excitotoxicity, calcium imbalance, membrane structure and integrity damage, etc. (Vorwerk et al 1999;Wu et al 2004;Huang et al 2007). Gangliosides may activate different Trk receptors by differentially affecting the release of neurotrophins (Rabin et al 2002).…”

“…The neuroprotective effects of GM1 ganglioside include several aspects such as reducing neuronal damage, preserving membrane structure and integrity, and restoring Ca(2+) homeostasis (Huang et al 2007;Vorwerk et al 1999;Wu et al 2004). It has been shown that GM1 facilitates the phenotypic recovery of motoneurons in the retrodorsal lateral nucleus of the spinal cord during aging and after axotomy (Goettl et al 2003).…”

Regulatory effects of insulin-like growth factor-1 on the expression of sensory neuropeptide mRNAs in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate

“…There has been convincing evidence that excessive extracellular accumulation of Glu is toxic to the central [11] and the peripheral neurons [12] . IGF-1 is a neurotrophic [13][14][15][16] and potent anti-apoptotic factor [17,18] .…”