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Published February 23, 2006 | public
Journal Article

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

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.

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.

Additional details

Created:
August 22, 2023
Modified:
October 25, 2023