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Cytokine and Anti-Inflammatory Drug Effects on Brain Trauma and Alzheimer’s Disease Pathology in Transgenic Mice

Patterson, P. H. (2000) Cytokine and Anti-Inflammatory Drug Effects on Brain Trauma and Alzheimer’s Disease Pathology in Transgenic Mice. In: Neuro-Immune Interactions in Neurologic and Psychiatric Disorders. Research and Perspectives in Neurosciences. Springer , Berlin, pp. 139-151. ISBN 978-3-642-64065-0.

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There is a continuous interaction between neurons, glia and inflammatory cells in the normal brain that is exacerbated following trauma or neurodegenerative disease. Cytokines mediate many of these interactions in injury and disease, and they may also play key roles in the developing and normal adult brain. Experiments using mice with targeted mutations in the gene for one of these cytokines, leukemia inhibitory factor (LIF), demonstrate that this protein is required for appropriate cell and behavioral responses to trauma in the nervous system. We find that LIF is induced by physical injury or chemically-induced inflammation, and in the absence of this cytokine, neuronal, astrocytic, microglial, neutrophil, macrophage and pain responses to these insults are strikingly altered. The specific effects of LIF deficiency depend critically on the site and type of injury, however. The inflammatory response can also be important in the establishment and/or progression of neurodegenerative disease. To study this we are using a transgenic mouse model of Alzheimer’s disease (AD). Preliminary results indicate that stressing the animals can strongly up-regulate the microglial reaction around senile plaques.

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Additional Information:© 2000 Springer-Verlag Berlin Heidelberg. Lisa Banner, Jing Han, Joanna Jankowsky, Ronit Lahav, Shigeki Sugiura, George Tofaris, Sara Tolaney and Rumina Zaman carried out the current work cited from our group. These projects are being supported by the NINDS, the Della Martin and the McGrath Foundations, Caltech Summer Undergraduate Research Fellowships, and the Human Frontiers in Science Program. I also acknowledge the technical and clerical support of Doreen McDowell and Floreen Rooks, and thank Jian Zhong, Sigrid Schwarz, Ronit Lahav and Joanna Jankowsky for their helpful comments on the manuscript.
Funding AgencyGrant Number
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
Della Martin FoundationUNSPECIFIED
McGrath FoundationUNSPECIFIED
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Subject Keywords:Leukemia Inhibitory Factor; Microglial Reaction; Sciatic Nerve Crush; Leukaemia Inhibitory Factor Receptor; Nerve Growth Factor Expression
Series Name:Research and Perspectives in Neurosciences
Record Number:CaltechAUTHORS:20200708-143705891
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104282
Deposited By: Tony Diaz
Deposited On:08 Jul 2020 22:00
Last Modified:16 Nov 2021 18:30

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