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More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Neuropathic pain is induced by injury or disease of the nervous system. Studies aimed at understanding the molecular pathophysiology of neuropathic pain have so far focused on a few known molecules and signaling pathways in neurons. However, the pathophysiology of neuropathic pain appears to be very complex and remains poorly understood. A global understanding of the molecular mechanisms involved in neuropathic pain is needed for a better understanding of the pathophysiology and treatment of neuropathic pain. Towards this end, we examined global gene expression changes as well as the pathobiology at the cellular level in a spinal nerve ligation neuropathic pain model using DNA microarray, quantitative real-time PCR and immunohistochemistry. We found that the behavioral hypersensitivity that is manifested in the persistent pain state is accompanied by previously undescribed changes in gene expression. In the DRG, we found regulation of: (1) immediate early genes; (2) genes such as ion channels and signaling molecules that contribute to the excitability of neurons; and (3) genes that are indicative of secondary events such as neuroinflammation. In addition, we studied gene regulation in both injured and uninjured DRG by quantitative PCR, and observed differential gene regulation in these two populations of DRGs. Furthermore, we demonstrated unexpected co-regulation of many genes, especially the activation of neuroinflammation markers in both the PNS and CNS. The results of our study provide a new picture of the molecular mechanisms that underlie the complexity of neuropathic pain and suggest that chronic pain shares common pathobiology with progressive neurodegenerative disease., (Copyright 2002 IBRO)

DNA chips are glass surfaces that represent thousands of DNA fragments arrayed at discrete sites. Hybridization of RNA or DNA-derived samples to DNA chips allows us to monitor expression of mRNAs or the occurrence of polymorphisms in genomic DNA. The technology holds great promise for identifying gene polymorphisms that predispose man to disease, gene regulation events involved in disease progression, and more-effective disease treatments.