Content and Traffic of Taurine in Hippocampal Reactive Astrocytes Fe`lix Junyent, 1 * Luisa De Lemos, 1,2 Juana Utrera, 2 Sonia Paco, 2 Fernando Aguado, 2 Antoni Camins, 1 Merce` Palla`s, 1 Rafael Romero, 3 and Carme Auladell 2 ABSTRACT: Taurine is one of the most abundant free amino acids in the mammalian central nervous system, where it is crucial to proper de- velopment. Moreover, taurine acts as a neuroprotectant in various dis- eases; in epilepsy, for example, it has the capacity to reduce or abolish seizures. In the present study, taurine levels has been determine in mice treated with Kainic Acid (KA) and results showed an increase of this amino acid in hippocampus but not in whole brain after 3 and 7 days of KA treatment. This increase occurs when gliosis was observed. More- over, taurine transporter (TAUT) was found in astrocytes 3 and 7 days after KA treatment, together with an increase in cysteine sulfinic acid decarboxylase (csd) mRNA, that codifies for the rate-limiting enzyme of taurine synthesis, in the hippocampus at the same times after KA treat- ment. Glial cultures enriched in astrocytes were developed to demon- strate that these cells are responsible for changes in taurine levels after an injury to the brain. The cultures were treated with proinflammatory cytokines to reproduce gliosis. In this experimental model, an increase in the immunoreactivity of GFAP was observed, together with an increase in CSD and taurine levels. Moreover, an alteration in the tau- rine uptake-release kinetics was detected in glial cells treated with cyto- kine. All data obtained indicate that astrocytes could play a key role in taurine level changes induced by neuronal damage. More studies are, therefore, needed to clarify the role taurine has in relation to neuronal death and repair. V VC 2010 Wiley-Liss, Inc. KEY WORDS: kainic acid; neuroprotection; astrogliosis; taurine transporter; epilepsy INTRODUCTION Among the several established epilepsy research models, the one based on injections of 2-carboxy-4 (1-methylethenyl)- 3- pirrolidinacetic acid, Kainic Acid (KA) both in rats and mice (for revisions see Ben-Ari and Cossart, 2000; Leite et al., 2002) has been widely used for the last two decades for its ability to replicate many of the phe- nomenological features of human temporal lobe epi- lepsy (TLE), the most common type of epilepsy in adults (Engel et al., 1989). Seizures cause extensive brain damage, often associated with an aberrant axo- nal reorganization, concomitant with an altered distri- bution of neurotransmitter receptor subtypes, an increase in reactivity of the glia (increased prolifera- tion and hypertrophy of astrocytes and microglia), molecular reorganization of the membrane and extrac- ellular matrix proteins, as well as failure of the cellular homeostasis (Niquet et al., 1994; Represa et al., 1995; Blumcke et al., 2000; Dudek et al., 2002; Lee et al., 2002; Pitkanen et al., 2002; Kondratyev and Gale, 2004; Cavazos et al., 2004). In particular, the pyrami- dal neurons readily degenerate following local or distal injections of KA, similarly to what occurs in TLE patients. Taurine (2-aminoethanesulfonic acid) is a b-amino acid, which is not incorporated into proteins and is found free in the organism. Taurine is derived from the diet or synthesized from cysteine, via cysteine sul- finate descarboxylase (CSD) and cysteine dioxygenase (CDO) (de la Rosa and Stipanuk, 1985; Tappaz et al., 1992); and most of this synthesis occurs in the liver (Wu, 1984; Tappaz et al., 1992). CSD is the rate-limiting enzyme in the synthesis of taurine and it is found mainly in astrocytes (Almarghini et al., 1991; Tappaz et al., 1994), although taurine is found in both neurons and astrocytes (Ottersen, 1988; Ottersen et al., 1988; Gragera et al., 1995; Magnusson, 1996). Precisely, taurine is one of the most abundant free amino acids in the mammalian brain and is critical for proper brain functioning (Huxtable, 1989, 1992). Despite no well known biological actions of taurine are described, is thought that high levels of taurine, which is presented in high ratio of intracellular to extracellular concentrations (ratio about 600:1) (Jacobson and Hamberger, 1985; Pasantes-Morales et al., 1986), are essential to do the proposed func- tions of this amino acid, such as osmoregulation (Solis et al., 1988; Nagelhus et al., 1993; Law, 1998a,b; Pasantes-Morales et al., 2000), membrane stabilization (Wright et al., 1986), neuroprotection from excito- toxic cell death (Huxtable, 1989; Trenkner, 1990; El Idrissi and Trenkner, 1999; El Idrissi et al., 2003), neuromodulation (Muramatsu et al., 1978; Dopico et al., 2006) and regulation of cellular calcium levels (Hendil and Hoffmann, 1974; Izumi et al., 1977; R.R. and C.A. contributed equally to this work. 1 Unitat de Farmacologia i Farmacogno` sia Facultat de Farma`cia, Institut de Biomedicina (IBUB), Centros de Investigacio´n Biome´dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barce- lona, Spain; 2 Departament de Biologia Cellular, Facultat de Biologia, Universitat de Barcelona, Spain; 3 Departament de Gene´tica, Facultat de Biologı ´a, Universitat de Barcelona, Spain Grant sponsor: Generalitat de Catalunya; Grant number: 2005SGR00830; Grant sponsor: Ministerio de Ciencia y Educacio´ n, Spain; Grant numbers: SAF2006-13092 and BFU2007-63209/BFI; Grant sponsor: Instituto de Salud Carlos III, Spain; Grant number: PI080400; Grant sponsor: Minis- terio de ciencia e innovacio´ n, Spain; Grant number: BFU2007-67889. *Correspondence to: Fe`lix Junyent Herena, Unitat de Farmacologia i Farmacogno` sia Facultat de Farma`cia, Institut de Biomedicina (IBUB), Centros de Investigacio´n Biome´dica en Red de Enfermedades Neurodege- nerativas (CIBERNED), Universitat de Barcelona, Spain. E-mail: felixjunyent@ub.edu or cauladell@ub.edu Accepted for publication 14 October 2009 DOI 10.1002/hipo.20739 Published online 15 January 2010 in Wiley Online Library (wileyonlinelibrary.com). HIPPOCAMPUS 21:185–197 (2011) V VC 2010 WILEY-LISS, INC.