Effect of neuroprotective therapies (hypothermia and cyclosporine a) on dopamine-induced apoptosis in human neuronal SH-SY5Y cells

Abstract

Hypothermia has a marked protective effect against apoptotic cell death induced by dopamine in a human neuroblastic cell line. The neuroprotective effect of CyA described with other apoptotic cell death stimuli was not demonstrated with our experimental conditions.

Neurotoxic/Neuroprotective Effects of Clozapine and the Positive Allosteric Modulator of mGluR2 JNJ-46356479 in Human Neuroblastoma Cell Cultures

“…It is important to note that most evidence of the neuroprotective effects of APs has been observed when cell cultures were exposed to different types of cell damage or stress [21,36,42]. In this study, we induced neurotoxicity with high concentrations of DA and GLU as reported in other studies with neuroblastoma cell lines [21,[43][44][45][46]. GLU and DA are essential neurotransmitters, but in excess in the extracellular environment, they may induce neuronal damage and degeneration, which is involved in the pathophysiology of schizophrenia.…”

“…GLU and DA are essential neurotransmitters, but in excess in the extracellular environment, they may induce neuronal damage and degeneration, which is involved in the pathophysiology of schizophrenia. Different mechanisms are involved in such neurotoxicity, including oxidative stress, oxytosis, mitochondrial damage and cellular apoptosis [13,43,45,46], which could be affected in different ways by CLZ and JNJ treatments. JNJ showed a potential neuroprotective effect in vitro, as it reduced the activation of caspase 3 induced by DA.…”

“…In order to explore molecular pathways that could be related to the neurotoxic/ neuroprotective effects of CLZ and JNJ observed in vitro, we analyzed changes in expression of key genes involved in survival and cell death that could be triggered by DA and GLU, such as apoptosis, necroptosis or oxytosis [43][44][45][46]. Interestingly, although the percentages of gene expression change were subtle in many cases, JNJ increased the expression of most glycolytic genes, especially that of PGK1 and PGAM1, and was capable of normalizing their expression when reduced by DA and GLU exposures.…”

“…Based on previous tests and other studies performed on neuroblastoma cell lines, apoptosis and cell death was induced with high concentrations of DA and GLU [21,[43][44][45]. Specifically, DA at 100 µM and GLU at 80 mM were used to induce similar reductions in cell viability.…”