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Neonatal rat microglia derived from different brain regions have distinct activation responses

Published online by Cambridge University Press:  03 August 2012

Aaron Y. Lai ,
Kamaldeep S. Dhami ,
Comfort D. Dibal  and
Kathryn G. Todd
Aaron Y. Lai
Affiliation:
Neurochemical Research Unit, Department of Psychiatry and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
Kamaldeep S. Dhami
Affiliation:
Neurochemical Research Unit, Department of Psychiatry and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
Comfort D. Dibal
Affiliation:
Neurochemical Research Unit, Department of Psychiatry and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
Kathryn G. Todd*
Affiliation:
Neurochemical Research Unit, Department of Psychiatry and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
*
Correspondence should be addressed to: Kathryn G. Todd, Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Alberta T6G 2K7, Canada phone: 1-780-492-6591 fax: 1-780-492-6841 email: kgtodd@ualberta.ca
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Abstract

The regional heterogeneity of neuronal phenotypes is a well-known phenomenon. Whether or not glia derived from different brain regions are phenotypically and functionally distinct is less clear. Here, we show that microglia, the resident immune cells of the brain, display region-specific responses for activating agents including glutamate (GLU), lipopolysaccharide (LPS) and adenosine 5′-triphosphate (ATP). Primary microglial cultures were prepared from brainstem (Brs), cortex (Ctx), hippocampus (Hip), striatum (Str) and thalamus (Thl) of 1-day-old rats and were shown to upregulate the release of nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) in a region- and activator-specific manner. With respect to ATP specifically, ATP-induced changes in microglial tumor necrosis factor-α (TNF-α) release, GLU uptake and purinergic receptor expression were also regionally different. When co-cultured with hypoxia (Hyp)-injured neurons, ATP-stimulated microglia from different regions induced different levels of neurotoxicity. These region-specific responses could be altered by pre-conditioning the microglia in a different neurochemical milieu, with taurine (TAU) being one of the key molecules involved. Together, our results demonstrate that microglia display a regional heterogeneity when activated, and this heterogeneity likely arises from differences in the environment surrounding the microglia. These findings present an additional mechanism that may help to explain the regional selectiveness of various brain pathologies.

Keywords

Neuroinflammationregionalitymicrogliagliaregional heterogeneity
Type
Research Article
Information
Neuron Glia Biology , Volume 7 , Special Issue 1: The Physiological Function of Microglia , February 2011 , pp. 5 - 16
Copyright
Copyright © Cambridge University Press 2012

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