ORIGINAL PAPER Glutamate-Dependent Transcriptional Regulation in Bergmann Glia Cells: Involvement of p38 MAP Kinase Rossana C. Zepeda Æ Iliana Barrera Æ Francisco Castela ´n Æ Abraham Soto-Cid Æ Luisa C. Herna ´ndez-Kelly Æ Esther Lo ´pez-Bayghen Æ Arturo Ortega Accepted: 26 December 2007 / Published online: 13 February 2008 Ó Springer Science+Business Media, LLC 2008 Abstract Glutamate (Glu) is the major excitatory neu- rotransmitter in the Central Nervous System (CNS). Ionotropic and metabotropic glutamate receptors (GluRs) are present in neurons and glial cells and are involved in gene expression regulation. Mitogen-activated proteins kinases (MAPK) are critical for all the membrane to nuclei signaling pathways described so far. In cerebellar Berg- mann glial cells, glutamate-dependent transcriptional regulation is partially dependent on p42/44 MAPK activity. Another member of this kinase family, p38 MAPK is activated by non-mitogenic stimuli through its Thr180/ Tyr182 phosphorylation and phosphorylates cytoplasmic and nuclear protein targets involved in translational and transcriptional events. Taking into consideration that the role of p38MAPK in glial cells is not well understood, we demonstrate here that glutamate increases p38 MAPK phosphorylation in a time and dose dependent manner in cultured chick cerebellar Bergmann glial cells (BGC). Moreover, p38 MAPK is involved in the glutamate- induced transcriptional activation in these cells. Ionotropic as well as metabotropic glutamate receptors participate in p38 MAPK activation. The present findings demonstrate the involvement of p38 MAPK in glutamate-dependent gene expression regulation in glial cells. Keywords p38 MAPK Á Gene expression regulation Á Transcriptional control Á Cerebellar glia Á Glutamate receptors Introduction L-Glutamate (Glu) is the main excitatory amino acid in Central Nervous System (CNS) of vertebrates where it exerts its effects through specific membrane receptors expressed in neurons and glia cells. Glutamate receptors (GluRs) are classified according to their transduction sys- tems into ionotropic and metabotropic receptors. Ionotropic receptors are ligand-gated ion channels involved in fast synaptic transmission and include N-metyl-D-aspartate (NMDA), a-amino-3-hidroxy-5-metyl-4-isoxazolepropio- nate (AMPA) and kainate (KA) receptors. In contrast, metabotropic receptors are G-protein coupled receptors able to modulate synaptic transmission through phospho- inositide metabolism (group I) or inhibition of adenylate cyclase (groups II and III) [1]. Bergmann glia cells (BGC) surround the synapses established between the terminals of the granule neurons, the parallel fibers and the Purkinje cells in the molecular layer of the cerebellum [2]. The repertoire of glutamatergic receptors in these cells includes both ionotropic and metabotropic Glu receptors [3, 4]. Glu released from the parallel fibers depolarizes the BGC triggering not only a significant Ca 2+ influx [5] but also a membrane to nuclei cascade that is implicated in transcriptional [6] and trans- lational [7] control. Interestingly, both ionotropic as well as metabotropic Glu receptors are involved in these processes and their activation lead to the recruitment and activation of transduction molecules [8, 9]. R. C. Zepeda Á I. Barrera Á F. Castela ´n Á L. C. Herna ´ndez-Kelly Á E. Lo ´pez-Bayghen Á A. Ortega (&) Departamento de Gene ´tica y Biologı ´a Molecular, Centro de Investigacio ´n y de Estudios Avanzados del Instituto Polite ´cnico Nacional (Cinvestav-IPN), Apartado Postal 14-740, Mexico, DF 07000, Mexico e-mail: arortega@cinvestav.mx A. Soto-Cid Facultad de Quı ´mica Farmace ´utica Biolo ´gica, Universidad Veracruzana, Xalapa, Veracruz, Mexico 123 Neurochem Res (2008) 33:1277–1285 DOI 10.1007/s11064-007-9580-x