Abstract：
:Cytokines are powerful mediators of biologic responses in the CNS and may contribute to cellular injury in pathophysiologic states. In order to better understand the actions of cytokines in the intact mammalian CNS, a transgenic approach was employed that targeted the expression of different cytokines to astrocytes in mice. Fusion gene constructs consisting of a GFAP expression vector into which was inserted the DNA encoding the cytokines interleukin-6 (IL-6), IL-3, or TNF-alpha were used to generate transgenic mice. Expression of the transgene-encoded cytokines in astrocytes was confirmed at both the RNA and protein levels. Transgenic mice were subject to multilevel analysis to determine the extent of structural and functional CNS alterations. Transgenic mice exhibited distinct adult-onset, chronic-progressive neurological disorders that correlated with the level and anatomic distribution of transgene-encoded cytokine expression. The principal findings were neurodegeneration and cognitive decline due to IL-6 expression, macrophage/microglial-mediated primary demyelination with motor disease resulting from IL-3 expression, and lymphocytic meningoencephalomyelitis with paralysis induced by TNF-alpha expression. These transgenic models (1) indicate that expression of cytokines per se in the intact CNS is pathogenic, with cytokine-specific neural cell injury leading to unique functional deficits; (2) recapitulate many of the structural and functional changes seen in human inflammatory neurological disorders; (3) provide a valuable tool for advancing our understanding of the CNS pathobiology of cytokines; and (4) offer a unique resource for the development and testing of therapies aimed at abrogating the harmful actions of these important mediators.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Campbell ILdoi
10.1111/j.1749-6632.1998.tb09552.xsubject
Has Abstractpub_date
1998-05-01 00:00:00pages
83-96eissn
0077-8923issn
1749-6632journal_volume
840pub_type
杂志文章,评审abstract：:Low- and high-frequency cortical oscillations play an important role in speech processing. Low-frequency neural oscillations in the delta (<4 Hz) and theta (4-8 Hz) bands entrain to the prosodic and syllabic rates of speech, respectively. Theta band neural oscillations modulate high-frequency neural oscillations in th...
journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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更新日期：1997-12-31 00:00:00
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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更新日期：2009-04-01 00:00:00
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
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journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
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更新日期：2005-04-01 00:00:00
