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Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development*

Published online by Cambridge University Press:  09 March 2009

Jonathan E. Cohen
Affiliation:
Nervous Systems Development and Plasticity Section, National Institutes of Health, NICHD, USA
R. Douglas Fields*
Affiliation:
Nervous Systems Development and Plasticity Section, National Institutes of Health, NICHD, USA
*
Correspondence should be addressed to: R. Douglas Fields, Nervous System Development and Plasticity Section, National Institutes of Health, NICHD Bldg. 35, Room 2A211, MSC 3713, 35 Lincoln Drive, Bethesda, MD 20892, USA phone: +1 301 480-3209 fax: +1 496-9630 email: fieldsd@mail.nih.gov

Abstract

Activity-dependent signaling between neurons and astrocytes contributes to experience-dependent plasticity and development of the nervous system. However, mechanisms responsible for neuron–glial interactions and the releasable factors that underlie these processes are not well understood. The pro-inflammatory cytokine, leukemia-inhibitory factor (LIF), is transiently expressed postnatally by glial cells in the hippocampus and rapidly up-regulated by enhanced neural activity following seizures. To test the hypothesis that spontaneous neural activity regulates glial development in hippocampus via LIF signaling, we blocked spontaneous activity with the sodium channel blocker tetrodotoxin (TTX) in mixed hippocampal cell cultures in combination with blockers of LIF and purinergic signaling. TTX decreased the number of GFAP-expressing astrocytes in hippocampal cell culture. Furthermore, blocking purinergic signaling by P2Y receptors contributed to reduced numbers of astrocytes. Blocking activity or purinergic signaling in the presence of function-blocking antibodies to LIF did not further decrease the number of astrocytes. Moreover, hippocampal cell cultures prepared from LIF −/− mice had reduced numbers of astrocytes and activity-dependent neuron–glial signaling promoting differentiation of astrocytes was absent. The results show that endogenous LIF is required for normal development of hippocampal astrocytes, and this process is regulated by spontaneous neural impulse activity through the release of ATP.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2009

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Footnotes

*

Marc R Freeman served as Editor-in-Chief for this manuscript.

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