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Development of a neurotoxicity test-system, using human post-mitotic, astrocytic and neuronal cell lines in co-culture.
Toxicol In Vitro. 2007 Oct; 21(7):1241-6.TV

Abstract

Astrocytes are essential for neuronal function and survival, so both cell types were included in a human neurotoxicity test-system to assess the protective effects of astrocytes on neurons, compared with a culture of neurons alone. The human NT2.D1 cell line was differentiated to form either a co-culture of post-mitotic NT2.N neuronal (TUJ1, NF68 and NSE positive) and NT2.A astrocytic (GFAP positive) cells (approximately 2:1 NT2.A:NT2.N), or an NT2.N mono-culture. Cultures were exposed to human toxins, for 4h at sub-cytotoxic concentrations, in order to compare levels of compromised cell function and thus evidence of an astrocytic protective effect. Functional endpoints examined included assays for cellular energy (ATP) and glutathione (GSH) levels, generation of hydrogen peroxide (H(2)O(2)) and caspase-3 activation. Generally, the NT2.N/A co-culture was more resistant to toxicity, maintaining superior ATP and GSH levels and sustaining smaller significant increases in H(2)O(2) levels compared with neurons alone. However, the pure neuronal culture showed a significantly lower level of caspase activation. These data suggest that besides their support for neurons through maintenance of ATP and GSH and control of H(2)O(2) levels, following exposure to some substances, astrocytes may promote an apoptotic mode of cell death. Thus, it appears the use of astrocytes in an in vitro predictive neurotoxicity test-system may be more relevant to human CNS structure and function than neuronal cells alone.

Authors+Show Affiliations

School of Life and Health Sciences, Aston University, Aston Street, Birmingham, B4 7ET, UK. wrighte@aston.ac.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17566694

Citation

Woehrling, E K., et al. "Development of a Neurotoxicity Test-system, Using Human Post-mitotic, Astrocytic and Neuronal Cell Lines in Co-culture." Toxicology in Vitro : an International Journal Published in Association With BIBRA, vol. 21, no. 7, 2007, pp. 1241-6.
Woehrling EK, Hill EJ, Coleman MD. Development of a neurotoxicity test-system, using human post-mitotic, astrocytic and neuronal cell lines in co-culture. Toxicol In Vitro. 2007;21(7):1241-6.
Woehrling, E. K., Hill, E. J., & Coleman, M. D. (2007). Development of a neurotoxicity test-system, using human post-mitotic, astrocytic and neuronal cell lines in co-culture. Toxicology in Vitro : an International Journal Published in Association With BIBRA, 21(7), 1241-6.
Woehrling EK, Hill EJ, Coleman MD. Development of a Neurotoxicity Test-system, Using Human Post-mitotic, Astrocytic and Neuronal Cell Lines in Co-culture. Toxicol In Vitro. 2007;21(7):1241-6. PubMed PMID: 17566694.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of a neurotoxicity test-system, using human post-mitotic, astrocytic and neuronal cell lines in co-culture. AU - Woehrling,E K, AU - Hill,E J, AU - Coleman,M D, Y1 - 2007/05/01/ PY - 2006/09/27/received PY - 2007/03/26/revised PY - 2007/04/16/accepted PY - 2007/6/15/pubmed PY - 2008/2/6/medline PY - 2007/6/15/entrez SP - 1241 EP - 6 JF - Toxicology in vitro : an international journal published in association with BIBRA JO - Toxicol In Vitro VL - 21 IS - 7 N2 - Astrocytes are essential for neuronal function and survival, so both cell types were included in a human neurotoxicity test-system to assess the protective effects of astrocytes on neurons, compared with a culture of neurons alone. The human NT2.D1 cell line was differentiated to form either a co-culture of post-mitotic NT2.N neuronal (TUJ1, NF68 and NSE positive) and NT2.A astrocytic (GFAP positive) cells (approximately 2:1 NT2.A:NT2.N), or an NT2.N mono-culture. Cultures were exposed to human toxins, for 4h at sub-cytotoxic concentrations, in order to compare levels of compromised cell function and thus evidence of an astrocytic protective effect. Functional endpoints examined included assays for cellular energy (ATP) and glutathione (GSH) levels, generation of hydrogen peroxide (H(2)O(2)) and caspase-3 activation. Generally, the NT2.N/A co-culture was more resistant to toxicity, maintaining superior ATP and GSH levels and sustaining smaller significant increases in H(2)O(2) levels compared with neurons alone. However, the pure neuronal culture showed a significantly lower level of caspase activation. These data suggest that besides their support for neurons through maintenance of ATP and GSH and control of H(2)O(2) levels, following exposure to some substances, astrocytes may promote an apoptotic mode of cell death. Thus, it appears the use of astrocytes in an in vitro predictive neurotoxicity test-system may be more relevant to human CNS structure and function than neuronal cells alone. SN - 0887-2333 UR - https://www.unboundmedicine.com/medline/citation/17566694/Development_of_a_neurotoxicity_test_system_using_human_post_mitotic_astrocytic_and_neuronal_cell_lines_in_co_culture_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0887-2333(07)00138-5 DB - PRIME DP - Unbound Medicine ER -