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The Journal of Neuroscience, November 7, 2007, 27(45):12255-12266; doi:10.1523/JNEUROSCI.3404-07.2007

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Cellular/Molecular
The Transcriptome and Metabolic Gene Signature of Protoplasmic Astrocytes in the Adult Murine Cortex

Ditte Lovatt,^1,2 Ursula Sonnewald,³ Helle S. Waagepetersen,⁴ Arne Schousboe,⁴ Wei He,¹ Jane H.-C. Lin,⁵ Xiaoning Han,¹ Takahiro Takano,¹ Su Wang,² Fraser J. Sim,² Steven A. Goldman,² and Maiken Nedergaard¹

¹Division of Glial Disease and Therapeutics, Department of Neurosurgery, and ²Department of Neurology, University of Rochester Medical Center, Rochester, New York 14642, ³Department of Neuroscience, Norwegian University of Science and Technology, 7491 Trondheim, Norway, ⁴Department of Pharmacology and Pharmacotherapy, Faculty of Pharmacological Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark, and ⁵Department of Pathology, New York Medical College, Valhalla, New York 10595

Correspondence should be addressed to either of the following: Dr. Steven A. Goldman, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, Email: Steven_Goldman{at}urmc.rochester.edu; or Dr. Maiken Nedergaard, Center for Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, Email: nedergaard{at}urmc.rochester.edu

Protoplasmic astrocytes are critically important to energy metabolism in the CNS. Our current understanding of the metabolic interactions between neurons and glia is based on studies using cultured cells, from which mainly inferential conclusions have been drawn as to the relative roles of neurons and glia in brain metabolism. In this study, we used functional genomics to establish the relative compartmentalization of neuronal and astrocytic metabolic pathways in the adult brain. To this end, fluorescence-activated cell sorting was used to directly isolate neurons and protoplasmic astrocytes from the cortex of adult mice. Microarray analysis showed that astrocytes and neurons each express transcripts predicting individual self-sufficiency in both glycolysis and oxidative metabolism. Surprisingly, most enzymes in the tricarboxylic acid (TCA) cycle were expressed at higher relative levels in astrocytes than in neurons. Mass spectrometric analysis of the TCA cycle intermediates confirmed that freshly isolated adult astrocytes maintained an active TCA cycle, whereas immuno-electron microscopy revealed that fine astrocytic processes encompassing synapses contained a higher density of mitochondria than surrounding cells. These observations indicate that astrocytes exhibit robust oxidative metabolism in the intact adult brain and suggest a prominent contribution of astrocytic metabolism to functional brain imaging, including BOLD (blood-oxygen level-dependent) functional magnetic resonance imaging signals.

Key words: FACS; microarray; glutamate; lactate; glycolysis; TCA cycle; mass spectrometry

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Received July 26, 2007; revised Sept. 10, 2007; accepted Sept. 20, 2007.

Correspondence should be addressed to either of the following: Dr. Steven A. Goldman, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, Email: Steven_Goldman{at}urmc.rochester.edu; or Dr. Maiken Nedergaard, Center for Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, Email: nedergaard{at}urmc.rochester.edu

This article has been cited by other articles:

				R. C. Reyes and V. Parpura Mitochondria Modulate Ca2+-Dependent Glutamate Release from Rat Cortical Astrocytes J. Neurosci., September 24, 2008; 28(39): 9682 - 9691. [Abstract] [Full Text] [PDF]

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