Comparison of Neurite Outgrowth With Neurofilament Protein Subunit Levels in Neuroblastoma Cells Following Mercuric Oxide Exposure

Abstract

1. The objectives of the study were to establish that inhibition of neuronal differentiation in culture (assessed by neurite outgrowth) can be used as a broad spectrum in vitro measure of neurotoxicity. 2. To establish whether a rapid measure of neurite outgrowth could be used. Thus the study examined the relationship between the degree of neurite outgrowth assessed directly by image analysis and neurofilament protein subunit levels measured by an ELISA. 3. SKNSH neuroblastoma cells, exposed for up to 6 days to mercuric chloride during initiation and continuation of differentiation, had lower levels of neurofilament proteins than unexposed cells. 4. Preliminary data from parallel examinations of neurite outgrowth assessed by image analysis and neurofilament protein subunit levels assessed by ELISA support a correlation when neurofilament protein levels are decreased by sub-cytotoxic doses of mercuric chloride in SKNSH cells.

Developmental neurotoxicity testing in vitro: Models for assessing chemical effects on neurite outgrowth

“…Neurofilament protein levels increase upon differentiation of cell lines (Yamazaki et al, 2005) and upon neurite outgrowth in primary cultures (Taniwaki and Schwartz, 1995). A correlation between chemical-induced reductions in neurite outgrowth and decreases in the level of neurofilament protein has been demonstrated in cell lines including NB41A3 cells (Abdulla and Campbell, 1993), SK-N-SH cells (Abdulla et al, 1995) and N2a cells (Flaskos et al, 2007). There may not be a direct relationship, however, between neurite length and neurofilament expression, as Cho and Tiffany-Castiglioni (2004) reported that decreased neurite length in SH-SY5Y cells in response to the pesticide exposure was associated with an upregulation of neurofilament protein.…”

Leveraging HCS in Neuroscience Drug Discovery

“…Another indirect approach to measuring neurite outgrowth is to perform an ELISA for neuronal cytoskeletal proteins (5). This approach assumes that as the neurites grow longer the neuron will produce more protein.…”

Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

“…aData on organotypic cultures from Braun et al (2006); Chalisova et al (2006); Chen et al (2005); Ghoumari et al (2005); Hechler et al (2006); Heck et al (2006); Neumann et al (1996); Overstreet et al (1997); Pinzon-Duarte et al (2004); Stoppini et al (1991); Strasser and Fischer (1995); Zimmer et al (2000).bData on re-aggregating brain cell culture from Braissant et al (2002); Braun et al (2006); Eskes et al (1999, 2002); Harry et al (1998); Honegger (1985); Honegger and Monnet-Tschudi (2001); Honegger and Richelson (1979); Monnet-Tschudi et al (1995a, 1995b, 1997b, 2000); Sales et al (2004); Seeds and Vater (1971); Zurich et al (2002, 2004).cData on primary dissociated culture from Bal-Price and Brown (2001); Demerens et al (1996); Goldin et al (2001); Howard et al (2005); Krause et al (2006); Lein et al (1995); Sah and Matsumoto (1987); Sass et al (2001); Veronesi (1992); van Pelt et al (2005); Yamamoto et al (2005).dData on immortalized human and rodent cell lines from Abdulla et al (1995); Greene (1978); Hong et al (2003); Pahlaman et al (1990); Parran et al (2001); Sachana et al (2001).…”

“…dData on immortalized human and rodent cell lines from Abdulla et al (1995); Greene (1978); Hong et al (2003); Pahlaman et al (1990); Parran et al (2001); Sachana et al (2001).…”