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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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References

REFERENCES

Brewer, G.J., Torricelli, J.R., Evege, E.K. and Price, P.J. (1993) Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination. Journal of Neuroscience Research 35, 567–576; doi:10.1002/jnr.490350513.CrossRefGoogle ScholarPubMed
Carson, M.J., Bilousova, T.V., Puntambekar, S.S., Melchior, B., Doose, J.M. and Ethell, I.M. (2007) A rose by any other name? The potential consequences of microglial heterogeneity during CNS health and disease. Neurotherapeutics 4, 571–579; doi:10.1016/j.nurt.2007.07.002.Google Scholar
Crain, J.M., Nikodemova, M. and Watters, J.J. (2009) Expression of P2 nucleotide receptors varies with age and sex in murine brain microglia. Journal of Neuroinflammation 6, 24; doi:10.1186/1742-2094-6-24.CrossRefGoogle ScholarPubMed
Damani, M.R., Zhao, L., Fontainhas, A.M., Amaral, J., Fariss, R.N. and Wong, W.T. (2011) Age-related alterations in the dynamic behavior of microglia. Aging Cell 10, 263–276; doi:10.1111/j.1474-9726. 2010.00660.x.CrossRefGoogle ScholarPubMed
de Haas, A.H., Boddeke, H.W. and Biber, K. (2008) Region-specific expression of immunoregulatory proteins on microglia in the healthy CNS. Glia 56, 888–894; doi:10.1002/glia.20663.CrossRefGoogle ScholarPubMed
Elkabes, S., DiCicco-Bloom, E.M. and Black, I.B. (1996) Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. Journal of Neuroscience 16, 2508–2521.CrossRefGoogle ScholarPubMed
Floden, A.M. and Combs, C.K. (2006) Beta-amyloid stimulates murine postnatal and adult microglia cultures in a unique manner. Journal of Neuroscience 26, 4644–4648; doi:10.1523/JNEUROSCI.4822-05.2006.CrossRefGoogle Scholar
Han, B.C., Koh, S.B., Lee, E.Y. and Seong, Y.H. (2004) Regional difference of glutamate-induced swelling in cultured rat brain astrocytes. Life Science 76, 573–583.CrossRefGoogle ScholarPubMed
Hanisch, U.K. and Kettenmann, H. (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nature Neuroscience 10, 1387–1394; doi:10.1038/nn1997.Google Scholar
Inoue, K. (2002) Microglial activation by purines and pyrimidines. Glia 40, 156–163; doi:10.1002/glia.10150.CrossRefGoogle ScholarPubMed
Lai, A.Y. and Todd, K.G. (2008) Differential regulation of trophic and proinflammatory microglial effectors is dependent on severity of neuronal injury. Glia 56, 259–270; doi:10.1002/glia.20610.CrossRefGoogle ScholarPubMed
Lawson, L.J., Perry, V.H., Dri, P. and Gordon, S. (1990) Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39, 151–170; doi:10.1016/0306-4522(90)90229-W.CrossRefGoogle ScholarPubMed
Lee, J.K., Tran, T. and Tansey, M.G. (2009) Neuroinflammation in Parkinson's Disease. Journal of Neuroimmune Pharmacology 4, 419–429; doi:10.1007/s11481-009-9176-0.CrossRefGoogle ScholarPubMed
Lockhart, B.P., Cressey, K.C. and Lepagnol, J.M. (1998) Suppression of nitric oxide formation by tyrosine kinase inhibitors in murine N9 microglia. British Journal of Pharmacology 123, 879–889; doi:10.1038/sj.bjp.0701664.CrossRefGoogle ScholarPubMed
Nakajima, K. and Kohsaka, S. (2004) Microglia: neuroprotective and neurotrophic cells in the central nervous system. Current Drug Targets – Cardiovascular and Hematological Disorders 4, 65–84; doi:10.2174/1568006043481284.CrossRefGoogle ScholarPubMed
Nakajima, K., Honda, S., Tohyama, Y., Imai, Y., Kohsaka, S. and Kurihara, T. (2001) Neurotrophin secretion from cultured microglia. Journal of Neuroscience Research 65, 322–331; doi:10.1002/jnr.1157.CrossRefGoogle ScholarPubMed
Persson, M., Brantefjord, M., Hansson, E. and Ronnback, L. (2005) Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-alpha. Glia 51, 111–120; doi:10.1002/glia.20191.CrossRefGoogle ScholarPubMed
Pocock, J.M. and Kettenmann, H. (2007) Neurotransmitter receptors on microglia. Trends in Neurosciences 30, 527–535; doi:10.1016/j.tins.2007.07.007.CrossRefGoogle ScholarPubMed
Raivich, G. (2005) Like cops on the beat: the active role of resting microglia. Trends in Neurosciences 28, 571–573; doi:10.1016/j.tins.2005.09.001.CrossRefGoogle ScholarPubMed
Ren, L., Lubrich, B., Biber, K. and Gebicke-Haerter, P.J. (1999) Differential expression of inflammatory mediators in rat microglia cultured from different brain regions. Brain Research. Molecular Brain Research 65, 198–205; doi:10.1016/S0169-328X(99)00016-9.Google Scholar
Saura, J., Tusell, J.M. and Serratosa, J. (2003) High-yield isolation of murine microglia by mild trypsinization. Glia 44, 183–189; doi:10.1002/glia.10274.CrossRefGoogle ScholarPubMed
Schlüter, K., Figiel, M., Rozyczka, J. and Engele, J. (2002) CNS region-specific regulation of glial glutamate transporter expression. European Journal of Neuroscience 16, 836–842; doi:10.1046/j.1460-9568.2002.02130.x.Google Scholar
Schmid, C.D., Sautkulis, L.N., Danielson, P.E., Cooper, J., Hasel, K.W., Hilbush, B.S. et al. (2002) Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. Journal of Neurochemistry 83, 1309–1320; doi:10.1046/j.1471-4159.2002.01243.x.CrossRefGoogle ScholarPubMed
Streit, W.J., Conde, J.R., Fendrick, S.E., Flanary, B.E. and Mariani, C.L. (2005) Role of microglia in the central nervous system's immune response. Neurological Research 27, 685–691.Google Scholar
Swayze, R.D., Lise, M.F., Levinson, J.N., Phillips, A. and El-Husseini, A. (2004) Modulation of dopamine mediated phosphorylation of AMPA receptors by PSD-95 and AKAP79/150. Neuropharmacology 47, 764–778; doi:10.1016/j.neuropharm.2004.07.014.Google Scholar
Tanaka, S., Kato, H. and Koike, T. (2000) Microglial response factor (MRF)-1: constitutive expression in ramified microglia and upregulation upon neuronal death induced by ischemia or glutamate exposure. Zoological Science 17, 571–578; doi:10.2108/zsj.17.571.CrossRefGoogle ScholarPubMed
Weiss, J.H. and Choi, D.W. (1991) Differential vulnerability to excitatory amino acid-induced toxicity and selective neuronal loss in neurodegenerative diseases. Canadian Journal of Neurological Sciences 18, 394–397.Google Scholar
Wolosker, H. (2007) NMDA receptor regulation by D-serine: new findings and perspectives. Molecular Neurobiology 36, 152–164; doi:10.1007/s12035-007-0038-6.Google Scholar
Wu, C.H., Chien, H.F., Chang, C.Y. and Ling, E.A. (1997) Heterogeneity of antigen expression and lectin labeling on microglial cells in the olfactory bulb of adult rats. Neuroscience Research 28, 67–75; doi:10.1016/S0168-0102(97)01178-4.CrossRefGoogle ScholarPubMed