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Glutamate elicits release of BDNF from basal forebrain astrocytes in a process dependent on metabotropic receptors and the PLC pathway

Published online by Cambridge University Press:  09 March 2009

Ying Y. Jean ,
Lauren D. Lercher  and
Cheryl F. Dreyfus
Ying Y. Jean
Affiliation:
Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert, Wood Johnson Medical School, Piscataway NJ, USA
Lauren D. Lercher
Affiliation:
Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert, Wood Johnson Medical School, Piscataway NJ, USA
Cheryl F. Dreyfus*
Affiliation:
Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert, Wood Johnson Medical School, Piscataway NJ, USA
*
Correspondence should be addressed to: Cheryl F. Dreyfus, Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert, Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA email: [email protected]
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Abstract

A key neurotrophin responsible for the survival and function of basal forebrain (BF) cholinergic neurons is brain-derived neurotrophic factor (BDNF). A number of studies now indicate that a source of this factor may be BF astrocytes. This study was designed to define the role of BF-astrocyte-derived BDNF on cholinergic neurons. Moreover, it investigated regulatory events that modulate BDNF content and release. In initial work BDNF derived from BF-astrocyte-conditioned medium (ACM) was found to increase both numbers of BF acetylcholinesterase (AChE+) cholinergic neurons and the cholinergic synthetic enzyme choline acetyltransferase (ChAT). Western blots, immunocytochemistry and pharmacological inhibition studies revealed that glutamate, through group I metabotropic glutamate receptors (mGluR), increases the intracellular levels of BDNF in BF astrocytes in culture, as well as its release. Furthermore, the release of BDNF is mediated by the actions of PLC, IP3 and internal stores of Ca2+. These results suggest that BF astrocytes serve as local sources of BDNF for cholinergic neurons, and that they may be regulated as such by the neuronal signal, glutamate, through the mediation of group I metabotropic receptors and the PLC pathway.

Keywords

Neurotrophingliasignaling pathwaymGluR
Type
Research Article
Information
Neuron Glia Biology , Volume 4 , Issue 1 , February 2008 , pp. 35 - 42
Copyright
Copyright © Cambridge University Press 2009

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