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Leukemia inhibitory factor is a key regulator of astrocytic, microglial and neuronal responses in a low-dose pilocarpine injury model

Holmberg, Kristina H. and Patterson, Paul H. (2006) Leukemia inhibitory factor is a key regulator of astrocytic, microglial and neuronal responses in a low-dose pilocarpine injury model. Brain Research, 1075 (1). pp. 26-35. ISSN 0006-8993. https://resolver.caltech.edu/CaltechAUTHORS:20160106-145242732

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Abstract

Insult to the central nervous system (CNS) induces many changes, including altered neurotransmitter expression, activation of astrocytes and microglia, neurogenesis and cell death. Cytokines and growth factors are candidates to be involved in astrocyte and microglial activation, and the up-regulation of glial fibrillary acidic protein (GFAP) is associated with brain damage. One of these candidates is leukemia inhibitory factor (LIF), a pro-inflammatory cytokine that is induced in astrocytes by brain damage or seizure. LIF also regulates expression of both neuropeptide Y (NPY) and galanin following peripheral nerve injury. To test the hypothesis that LIF regulates astrocyte, microglial and neuropeptide responses to a mild insult, we used a low-dose pilocarpine model to induce a brief seizure in LIF knock-out (KO) mice. Compared to wild type mice, the LIF KO mouse displays reduced astrocyte and microglial activation in the hippocampus. In addition, LIF KO mice display dramatically altered NPY, but not galanin, expression in response to injury. Thus, LIF is required for normal glial responses to brain damage, and, as in the periphery, LIF regulates NPY expression in the CNS.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.brainres.2005.12.103DOIArticle
http://www.sciencedirect.com/science/article/pii/S0006899305020305PublisherArticle
Additional Information:© 2006 Elsevier B.V. Accepted 29 December 2005; Available online 3 February 2006. We are grateful to Drs. T. Hökfelt (Karolinska Institutet, Sweden) and E. Theodorsson (Linköping University Hospital, Sweden) for the generous gift of galanin antibody. K.H.H. was supported by a Postdoctoral Research Fellowship from Svenska Sällskapet för Medicinsk Forskning, and the research was supported by grants from the NINDS, the McGrath Foundation and the Gimble Neuroscience Discovery Fund to P.H.P. We are also grateful to Dr. J. Jankowsky for providing useful data early in this study.
Funders:
Funding AgencyGrant Number
Svenska Sällskapet för Medicinsk ForskningUNSPECIFIED
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
McGrath FoundationUNSPECIFIED
Gimble Neuroscience Discovery FundUNSPECIFIED
Subject Keywords:Neuropeptide Y; Hippocampus; Pilocarpine; LIF; Seizure; IL-6
Issue or Number:1
Record Number:CaltechAUTHORS:20160106-145242732
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160106-145242732
Official Citation:Kristina H. Holmberg, Paul H. Patterson, Leukemia inhibitory factor is a key regulator of astrocytic, microglial and neuronal responses in a low-dose pilocarpine injury model, Brain Research, Volume 1075, Issue 1, 23 February 2006, Pages 26-35, ISSN 0006-8993, http://dx.doi.org/10.1016/j.brainres.2005.12.103. (http://www.sciencedirect.com/science/article/pii/S0006899305020305)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63439
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:07 Jan 2016 00:59
Last Modified:03 Oct 2019 09:28

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