PMID- 24512234
OWN - NLM
STAT- MEDLINE
DCOM- 20140415
LR  - 20190518
IS  - 0261-1929 (Print)
IS  - 0261-1929 (Linking)
VI  - 41
IP  - 6
DP  - 2013 Dec
TI  - Brain-derived neurotrophic factor as an indicator of chemical neurotoxicity: an 
      animal-free CNS cell culture model.
PG  - 503-11
AB  - Recent changes to the legislation on chemicals and cosmetics testing call for a 
      change in the paradigm regarding the current 'whole animal' approach for 
      identifying chemical hazards, including the assessment of potential neurotoxins. 
      Accordingly, since 2004, we have worked on the development of the integrated 
      co-culture of post-mitotic, human-derived neurons and astrocytes (NT2.N/A), for 
      use as an in vitro functional central nervous system (CNS) model. We have used it 
      successfully to investigate indicators of neurotoxicity. For this purpose, we 
      used NT2.N/A cells to examine the effects of acute exposure to a range of test 
      chemicals on the cellular release of brain-derived neurotrophic factor (BDNF). It 
      was demonstrated that the release of this protective neurotrophin into the 
      culture medium (above that of control levels) occurred consistently in response 
      to sub-cytotoxic levels of known neurotoxic, but not non-neurotoxic, chemicals. 
      These increases in BDNF release were quantifiable, statistically significant, and 
      occurred at concentrations below those at which cell death was measureable, which 
      potentially indicates specific neurotoxicity, as opposed to general cytotoxicity. 
      The fact that the BDNF immunoassay is non-invasive, and that NT2.N/A cells retain 
      their functionality for a period of months, may make this system useful for 
      repeated-dose toxicity testing, which is of particular relevance to cosmetics 
      testing without the use of laboratory animals. In addition, the production of 
      NT2.N/A cells without the use of animal products, such as fetal bovine serum, is 
      being explored, to produce a fully-humanised cellular model.
CI  - 2013 FRAME.
FAU - Woehrling, Elizabeth K
AU  - Woehrling EK
AD  - Mechanisms of Toxicity Group, School of Life and Health Sciences, Aston 
      University, Birmingham, UK.
FAU - Hill, Eric J
AU  - Hill EJ
FAU - Nagel, David
AU  - Nagel D
FAU - Coleman, Michael D
AU  - Coleman MD
LA  - eng
PT  - Journal Article
PL  - England
TA  - Altern Lab Anim
JT  - Alternatives to laboratory animals : ATLA
JID - 8110074
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - *Animal Testing Alternatives
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Differentiation
MH  - Central Nervous System/*drug effects/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
EDAT- 2014/02/12 06:00
MHDA- 2014/04/16 06:00
CRDT- 2014/02/12 06:00
PHST- 2014/02/12 06:00 [entrez]
PHST- 2014/02/12 06:00 [pubmed]
PHST- 2014/04/16 06:00 [medline]
AID - 10.1177/026119291304100613 [doi]
PST - ppublish
SO  - Altern Lab Anim. 2013 Dec;41(6):503-11. doi: 10.1177/026119291304100613.