Abstract

Nucleo CMP Forte(R) is a nucleotide-based drug consisting of cytidinemonophosphate, uridinemonophosphate, uridin-ediphosphate and uridinetriphosphate. It has been prescribed for peripheral nervous system disorders, such as lum-bosciatalgia, diabetic or alcoholic polyneuropathy, or trigeminal neuralgia. Its effects on brain pathologies has re-ceived little attention. We examined its neuroprotective effects on cell toxicity induced by glutamate excitotoxicity or by 1-methyl-4-phenyl-pyridinium (MPP+), an in vitro cell model of Parkinson’s disease. We used the human dopaminergic cell line SH-SY5Y and a primary culture of rat cortical cells pre-treated with the drug for 24 hours and then exposed to MPP+ or glutamate at a range of concentrations. Cell viability was measured at different times. Nucleo CMP Forte(R) pre-treatment significantly increased the rate of cell division in SH-SY5Y cells, as well as the synthesis of triglycerides and phospholipids. More interestingly, drug pre-treatment significantly reduced MPP+- and glutamate-induced cell death in SH-SY5Y cells and in rat cortical cells. These results indicate that the nucleotides included in Nucleo CMP Forte(R) are promising therapeutic molecules for the prevention of neuronal death in brain caused by focal ischemia, Parkinson’s disease or other neurodegenerative pathologies.

Highlights

  • Injury in the brain triggers an abnormal release of glutamate and other excitatory aminoacids that contribute significantly to neuronal death [1,2]

  • We examined its neuroprotective effects on cell toxicity induced by glutamate excitotoxicity or by 1methyl-4-phenyl-pyridinium (MPP+), an in vitro cell model of Parkinson’s disease

  • Drug pre-treatment significantly reduced MPP+- and glutamate-induced cell death in SH-SY5Y cells and in rat cortical cells. These results indicate that the nucleotides included in Nucleo CMP Forte® are promising therapeutic molecules for the prevention of neuronal death in brain caused by focal ischemia, Parkinson’s disease or other neurodegenerative pathologies

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Summary

Introduction

Injury (trauma or ischemia) in the brain triggers an abnormal release of glutamate and other excitatory aminoacids that contribute significantly to neuronal death [1,2]. This phenomenon, named excitotoxicity, has been implicated in epileptic seizures [3] and various chronic and progressive neurodegenerative diseases, such as Huntington’s chorea, Alzheimer’s disease, and Parkinson’s disease [4]. The present study demonstrates the neuroprotective effects of Nucleo CMP Forte® in two in vitro models of neuronal death: glutamate excitotoxicity and MPP+ toxicity

Materials and Reagents
SH-SY5Y Cell Culture
Primary Cultures of Rat Cortical Cell
Cell Treatment
Cell Viability Assay
Enzymatic Colorimetric Assay
Statistical Analysis
Cytotoxicity of the Nucleotide-Based Drug
Effects of the Nucleotide-Based Drug on SH-SY5Y Cell Growth
Effects of the Nucleotide-Based Drug on SH-SY5Y Lipid Concentration
Discussion
Conclusions
Full Text
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