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Author (up) Albuquerque, E.X.; Pereira, E.F.R.; Alkondon, M.; Rogers, S.W. file  url
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  Title Mammalian nicotinic acetylcholine receptors: from structure to function Type Journal Article
  Year 2009 Publication Physiological Reviews Abbreviated Journal Physiol Rev  
  Volume 89 Issue 1 Pages 73-120  
  Keywords Alzheimer Disease/physiopathology; Animals; Brain/physiology; Disease Models, Animal; Gene Expression Regulation/physiology; Humans; Parkinson Disease/physiopathology; Receptors, Nicotinic/*chemistry/*physiology  
  Abstract The classical studies of nicotine by Langley at the turn of the 20th century introduced the concept of a “receptive substance,” from which the idea of a “receptor” came to light. Subsequent studies aided by the Torpedo electric organ, a rich source of muscle-type nicotinic receptors (nAChRs), and the discovery of alpha-bungarotoxin, a snake toxin that binds pseudo-irreversibly to the muscle nAChR, resulted in the muscle nAChR being the best characterized ligand-gated ion channel hitherto. With the advancement of functional and genetic studies in the late 1980s, the existence of nAChRs in the mammalian brain was confirmed and the realization that the numerous nAChR subtypes contribute to the psychoactive properties of nicotine and other drugs of abuse and to the neuropathology of various diseases, including Alzheimer's, Parkinson's, and schizophrenia, has since emerged. This review provides a comprehensive overview of these findings and the more recent revelations of the impact that the rich diversity in function and expression of this receptor family has on neuronal and nonneuronal cells throughout the body. Despite these numerous developments, our understanding of the contributions of specific neuronal nAChR subtypes to the many facets of physiology throughout the body remains in its infancy.  
  Call Number Serial 1876  
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Author (up) Henn, A.; Lund, S.; Hedtjarn, M.; Schrattenholz, A.; Porzgen, P.; Leist, M. file  url
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  Title The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation Type Journal Article
  Year 2009 Publication Altex Abbreviated Journal Altex  
  Volume 26 Issue 2 Pages 83-94  
  Keywords Animal Testing Alternatives/*methods; Animals; Astrocytes/physiology; Brain/*pathology; Cell Line; Culture Media, Conditioned; Cytokines/metabolism; Gene Expression Regulation/physiology; Inflammation/*pathology; Lipopolysaccharides/toxicity; Mice; Microglia/*cytology/*physiology; NF-kappa B/metabolism; Nitrites/metabolism; RNA, Messenger/genetics/metabolism  
  Abstract The role of microglia in neurodegeneration, toxicology and immunity is an expanding area of biomedical research requiring large numbers of animals. Use of a microglia-like cell line would accelerate many research programmes and reduce the necessity of continuous cell preparations and animal experimentation, provided that the cell line reproduces the in vivo situation or primary microglia (PM) with high fidelity. The immortalised murine microglial cell line BV-2 has been used frequently as a substitute for PM, but recently doubts were raised as to their suitability. Here, we re-evaluated strengths and potential short-comings of BV-2 cells. Their response to lipopolysaccharide was compared with the response of microglia in vitro and in vivo. Transcriptome (480 genes) and proteome analyses after stimulation with lipopolysaccharide indicated a reaction pattern of BV-2 with many similarities to that of PM, although the average upregulation of genes was less pronounced. The cells showed a normal regulation of NO production and a functional response to IFN-gamma, important parameters for appropriate interaction with T cells and neurons. BV-2 were also able to stimulate other glial cells. They triggered the translocation of NF-kappaB, and a subsequent production of IL-6 in astrocytes. Thus, BV-2 cells appear to be a valid substitute for PM in many experimental settings, incuding complex cell-cell interaction studies.  
  Call Number Serial 163  
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