GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Ghrelin protects spinal cord motoneurons against chronic glutamate-induced excitotoxicity via ERK1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3β pathways.
Lim. Eunjin E; Lee. Sungyoub S; Li. Endan E; Kim. Yumi Y; Park. Seungjoon S
Key Findings
- Motor neurons in spinal cord cultures express the ghrelin receptor.
- Ghrelin treatment significantly reduced neuron loss caused by chronic glutamate exposure.
- The protective effect required activation of ERK1/2 and PI3K/Akt signaling and was blocked by a ghrelin‑receptor antagonist or pathway inhibitors.
Practical Outcomes
- The study suggests ghrelin may have neuroprotective properties that could be relevant for conditions like ALS, but the evidence is limited to cell‑culture experiments. Biohackers should view this as early‑stage science—not a ready‑to‑use protocol—and await animal or human data before considering ghrelin supplementation for brain or spinal health.
Summary
In a lab model of spinal cord tissue, the hormone ghrelin was shown to protect motor neurons from damage caused by excess glutamate. The protection depended on ghrelin binding to its receptor and activating specific cell‑signaling pathways (ERK1/2 and PI3K/Akt), which in turn turned off a harmful enzyme called GSK‑3β. Blocking the ghrelin receptor or those pathways stopped the protective effect.
Abstract
Excitotoxic degeneration of spinal cord motoneurons has been proposed as a pathogenic mechanism in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R) 1a, functions as a neuroprotective factor in various animal models of neurodegenerative diseases. In this study, the potential neuroprotective effects of ghrelin against chronic glutamate-induced cell death were studied by exposing organotypic spinal cord cultures (OSCC) to threohydroxyaspartate (THA), as a model of excitotoxic motoneuron degeneration. Ghrelin receptor was expressed on spinal cord motoneurons. Exposure of OSCC to THA for 3 weeks resulted in a significant loss of motoneurons. However, THA-induced loss of motoneurons was significantly reduced by treatment of ghrelin. Exposure of OSCC to the receptor-specific antagonist D-Lys-3-GHRP-6 abolished the protective effect of ghrelin against THA. Treatment of spinal cord cultures with ghrelin caused rapid phosphorylation of extracellular signal-regulated kinase 1/2, Akt, and glycogen synthase kinase-3β (GSK-3β). The effect of ghrelin on motoneuron survival was blocked by the MEK inhibitor PD98059 and the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. Taken together, these findings indicate that ghrelin has neuroprotective effects against chronic glutamate toxicity by activating the MAPK and PI3K/Akt signaling pathways and suggest that administration of ghrelin may have the potential therapeutic value for the prevention of motoneuron degeneration in human ALS. Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3β in motoneurons contributes to the protective effect of ghrelin.
Study Information
pubmed
2011
2011-04-20T00:00:00.000Z
10.1016/j.expneurol.2011.04.003
40
59