Evaluation of the neuroprotective effects of growth hormone secretagogues and glycosaminoglycans in an in vitro model of glutamate toxicity

Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS) and several evidences have shown that it is implicated in the pathogenesis of different neurodegenerative diseases, such as amyotrophic lateral sclerosis, Huntington’s disease and Alzheimer’s disease. Glycosaminoglycans (GAGs) are a group of sulphated and linear polysaccharides that exert a variety of biological functions, such as allowing the diffusion of soluble signalling molecules, like insulin-like growth factor-1 (IGF-1), within the extracellular matrix. Previous studies demonstrated that GAGs enhanced the neuroprotective effects of IGF-1 in wobbler mice, leading to a significant increase of motor neuron survival. However, given the high tumorigenic potential of exogenous IGF-1 administration, alternative methods to increase endogenous IGF-1 expression should be develop. Growth hormone secretagogues (GHS) are a family of peptides that stimulates the secretion of growth hormone and IGF-1, and exerts protective effects against β-amyloid cytotoxicity. Based on these data, the purpose of the study was to evaluate the neuroprotective role of the combination GHS and GAGs against glutamate toxicity in the GT1-7 mouse hypothalamic neuronal cell line. Our preliminary results suggest that GHS and GAGs, given alone or in combination, counteracted the reduction of cell viability induced by the incubation with glutamate. Moreover, glutamate treatment induced the activation of the proinflammatory transcription factor NF-κB, which was suppressed by the incubation with both GAGs and GHS. In conclusion, our results suggest that GHS and GAGs co-administration exerted neuroprotective and anti-inflammatory activities against glutamate-induced toxicity in GT1-7 neuronal cells. Further experiments are needed to identify the molecular mechanisms underlying the neuroprotective effects of GHS/GAGs association, so that they could be considered as a novel therapeutical approach in the treatment of neurodegenerative disease.