Highly Differential Expression of SN1, a Bidirectional Glutamine Transporter, in Astroglia and Endothelium in the Developing Rat Brain JEAN-LUC BOULLAND, AMINA RAFIKI, LINE M. LEVY, JON STORM-MATHISEN, AND FARRUKH A. CHAUDHRY* Department of Anatomy, Institute of Basic Medical Sciences and Centre for Molecular Biology and Neuroscience, University of Oslo, Oslo, Norway KEY WORDS SN1; glutamine; glutamate; transporter; synaptogenesis; blood-brain barrier ABSTRACT The transmitters glutamate and GABA also subserve trophic action and are required for normal development of the brain. They are formed from glutamine, which may be synthesized in glia or extracted from the blood. In the adult, the glutamine transporter SN1 is expressed in the astroglia. SN1 works in both directions, depending on the concentration gradients of its substrates and cotransported ions, and is thought to regulate extracellular glutamine and to supply the neurons with the transmitter precursor. In this article, we have quantified the expression and studied the localization of SN1 at different developmental stages. SN1 is expressed in astroglia throughout the CNS from embryonic stages through adulthood. No indication of SN1 staining in neu- ronal elements has been obtained at any stage. Quantitative immunoblotting of whole brain extracts demonstrates increasing expression of SN1 from P0, reaching a peak at P14, twice the adult level. A moderate and slower rise and fall of the expression levels of SN1 occurs in the cerebellum. Strong transient SN1-like staining is also found in Bergmann glia and vascular endothelium in the first postnatal weeks. Strong intracel- lular staining in the same time period suggests a high rate of SN1 synthesis in the early postnatal period. This coincides with the increasing levels of glutamate and GABA in the CNS and with the time course of synaptogenesis. This study suggests that the expres- sion of SN1 is highly regulated, correlating with the demand for glutamine during the critical period of development. GLIA 41:260 –275, 2003. © 2003 Wiley-Liss, Inc. INTRODUCTION Neurotransmitters are endogenous regulators of neurogenesis, neural migration, and synaptogenesis (Spencer et al., 1998). Increased levels of the transmit- ters and their specific receptors have been detected especially during the critical period for synaptogenesis in the rat brain (Kwong et al., 2000). A lack of activa- tion or inhibition of these receptors leads to patholog- ical development or cell death (Monti and Contestabile, 2000). Glutamate and GABA are the most abundant excitatory and inhibitory neurotransmitters in the brain, respectively. These transmitters are generated from glutamine, which is generally believed to be syn- thesized in the glia. Thus, impairment of glutamine transport from glia to the neurons during ontogenesis could be a limiting factor leading to reduced levels of *Correspondence to: Farrukh A. Chaudhry, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105 Blindern, N-0317 Oslo, Norway. Received 1 July 2002; Accepted 17 October 2002 DOI 10.1002/glia.10188 GLIA 41:260 –275 (2003) © 2003 Wiley-Liss, Inc.