Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
GABA(A) receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity
Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas, CSIC-IDIBAPS, Barcelona, and CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas, CSIC-IDIBAPS, Barcelona, and CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas, CSIC-IDIBAPS, Barcelona,.
Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas, CSIC-IDIBAPS, Barcelona,.
Show others and affiliations
2010 (English)In: Neurotoxicology and Teratology, ISSN 0892-0362, E-ISSN 1872-9738, Vol. 32, 52-61 p.Article in journal (Refereed) Published
Abstract [en]

Toxicity risk assessment for chemical-induced human health hazards relies mainly on data obtained from animal experimentation, human studies and epidemiology. In vitro testing for acute toxicity based on cytotoxicity assays predicts 70 - 80% of rodent and human toxicity. The nervous system is particularly vulnerable to chemical exposure which may result in different toxicity features. Acute human toxicity related to adverse neuronal function is usually a result of over-excitation or depression of the nervous system. The major molecular and cellular mechanisms involved in such reactions include GABAergic, glutamatergic and cholinergic neurotransmission, regulation of cell and mitochondrial membrane potential, and those critical for maintaining central nervous system functionality, such as controlling cell energy. In this work, a set of chemicals that are used in pharmacy, industry, biocide treatments or are often abused by drug users are tested for their effects on GABA(A) receptor activity, GABA and glutamate transport, cell membrane potential and cell viability in primary neuronal cultures. GABA(A) receptor function was inhibited by compounds for which seizures have been observed after severe human poisoning. Commonly abused drugs inhibit GABA uptake but not glutamate uptake. Most neurotoxins altered membrane potential. The GABA(A) receptor, GABA uptake and cell membrane potential assays were those that identified the highest number of chemicals as toxic at low concentrations. These results show that in vitro cell assays may identify compounds that produce acute neurotoxicity in humans, provided that in vitro models expressing neuronal targets relevant for acute neural dysfunctions are used.

Place, publisher, year, edition, pages
2010. Vol. 32, 52-61 p.
Keyword [en]
Neurotoxicity, In vitro, Primary neuronal cultures, GABA, GABAA receptor, Cell membrane potential
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:su:diva-32267DOI: 10.1016/j.ntt.2009.01.010ISI: 000274881500007PubMedID: 19602384OAI: oai:DiVA.org:su-32267DiVA: diva2:279975
Available from: 2009-12-07 Created: 2009-12-07 Last updated: 2017-12-12Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Forsby, Anna
By organisation
Department of Neurochemistry
In the same journal
Neurotoxicology and Teratology
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 42 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf