Systemic interleukin-1 beta decreases brain-derived neurotrophic factor messenger RNA expression in the rat hippocampal formation.
Brain-derived neurotrophic factor is selectively expressed at relatively high levels in the rat hippocampal formation (for review, see Ref. 12; see also Refs 8, 13, 19, 20, 27) where it is thought to be involved in mechanisms of neurodegeneration and/or neural protection related to the plasticity of hippocampal neurons. Functional responses to brain-derived neurotrophic factor appear to be mediated by a tyrosine receptor kinase B with the possible involvement of the p75 low-affinity nerve growth factor receptor protein. Among the many characteristics of Alzheimer's disease is an upregulation of immune mediators in and around senile plaques in Alzheimer's disease. Recently, interleukin-1 has been shown to be detrimental to the long-term survival of embryonic hippocampal neurons in culture. Thus, if the same occurs in vivo, it is possible that the accumulation of interleukin-1 in Alzheimer's disease hippocampus may be responsible for altered hippocampal neuron synaptic plasticity. This may occur either by a direct action of interleukin-1 on hippocampal neurons or possibly indirectly by stimulating beta-amyloid production. Other indirect mechanisms may involve growth or survival factors such as the neurotrophin brain-derived neurotrophic factor which is thought to play an important role in the plastic responses of hippocampal neurons. A recent study showed that brain-derived neurotrophic factor mRNA is selectively decreased in the dentate gyrus in Alzheimer's disease. The reason(s) for the decrease of brain-derived neurotrophic factor mRNA is not known, but one possibility may be associated with the enhanced expression of interleukin-1 in the hippocampus of Alzheimer's disease patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Neurogerontology, Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
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Lapchak
D M
DM
Araujo
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Hefti
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009410:Nerve Degeneration / Q000502:physiology; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases