1 3 ORIGINAL ARTICLE Ann Nucl Med (2009) 23:143–147 DOI 10.1007/s12149-008-0216-2 S. Hirose (*) · S. Momosaki · R. Hosoi · K. Abe · O. Inoue Division of Health Sciences, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan e-mail: hirose@sahs.med.osaka-u.ac.jp A. Gee Department of Chemistry, Chemical Biology Center, Imperial College of London, London, UK Role of NMDA receptor upon [ 14 C]acetate uptake into intact rat brain Shinichiro Hirose · Sotaro Momosaki · Rie Hosoi Kohji Abe · Antony Gee · Osamu Inoue Introduction It has been well documented that glial cells selectively take up acetate both in vitro and in vivo [1, 2], which is converted to acetyl CoA in glial cells. This selective uptake of acetate by glial cells seems mainly to reflect differential transport mechanisms for monocarboxylates between glia and neurons [3]; MCT-1 and MCT-2, two different monocarboxylate transporters (MCT), are expressed predominantly in glia and neurons, respec- tively [4]. We earlier reported that [ 14 C]acetate uptake was significantly (more than 80%) decreased by micro- infusion of fluorocitrate (1 nmol/μl), a selective glial toxin [5], into the striatum of the rat brain, despite a regional increase in blood flow [6]. These results strongly indicated that [ 14 C]acetate uptake in the brain was flow independent and might reflect tricarboxylic acid (TCA) cycle activity in glial cells in the intact brain. We also recently found that [ 14 C]acetate uptake in the rat brain was decreased by a short-term occlusion (from 3 min to 30 min) of the middle cerebral artery and reperfusion [7]. This reduction in [ 14 C]acetate uptake in the rat brain induced by a short-term ischemia was transient, and almost completely recovered to control levels within 30 min following reperfusion (30 min occlusion). However, the molecular mechanism for regulation of acetate uptake into glial cells is unknown. Glutamate plays an essential role in ischemic brain damage [8, 9], and it also enhances glucose utilization in glial cells [10]. Therefore, glutamate may possibly regulate acetate uptake into glial cells. The objective of this study is to clarify whether N-methyl-D-aspartate (NMDA) recep- tors are involved in the regulation of [ 14 C]acetate uptake in glial cells in the intact rat brain. We examined the effect of a microinjection of ibotenic acid (IBO) (NMDA Received: 26 September 2008 / Accepted: 6 November 2008 © The Japanese Society of Nuclear Medicine 2009 Abstract Objective To clarify the role of N-methyl-D-aspartate (NMDA) receptors upon [ 14 C]acetate uptake in the rodent central nervous system (CNS), ibotenic acid (IBO) was infused into the right striatum of the rat brain. Methods Autoradiograms of [ 14 C]acetate uptake in the brain for 2 h following the infusion of IBO (10 μg/μl) were obtained in both non-treated and MK-801 (1 mg/kg, i.v.) pretreated rats. The effect of MK-801 on [ 14 C]acetate uptake in the normal rat brain was also studied. Results Infusion of IBO significantly decreased [ 14 C]acetate uptake in the infused side of the striatum. The expression of monocarboxylate transporter-1 was not altered, suggesting that the activity of tricarboxylic acid (TCA) cycle in glial cells might be depressed. Pre- treatment with MK-801 completely blocked the decreas- ing effect of IBO on [ 14 C]acetate uptake. MK-801 also increased [ 14 C]acetate uptake in the whole brain of normal rats. Conclusions These results indicate the important roles of NMDA receptors on [ 14 C]acetate uptake in the intact rat brain. Keywords Glia · [ 14 C]acetate · MK-801 · Ibotenic acid · Rat