Evidence for serotonin influencing the thalamic infiltration of mast cells in rat D. Dubayle a, * , J. Servie `re b , D. Mene ´trey a a CNRS UMR 8119 Neurophysique et physiologie, Universite ´ Rene ´ Descartes, UFR Biome ´dicale, 45 rue des Saints-Pe `res, 75270 Paris Cedex 06, France b INRA INAPG, De ´partement des Sciences Animales, 16 rue Claude Bernard, 75231 Paris Cedex 05, France Received 11 June 2004; received in revised form 24 August 2004; accepted 30 August 2004 Abstract Serotonin (5-HT) is involved in neuroimmunomodulation. We analyzed the effects of sumatriptan, a 5-HT 1B/1D receptor agonist, and ondansetron, a 5-HT 3 receptor antagonist, on thalamic mast cell (TMC) population, the only immunocytes known to infiltrate the brain in physiological conditions. Only sumatriptan was effective, significantly increasing TMC numbers versus controls, and especially those containing 5-HT. 5-HT 1B receptors are concentrated in the median eminence on non-serotonergic axonal endings, probably hypothalamic terminal fibers, involved in hypothalamic–pituitary neuroendocrine modulating processes. TMC variations could reflect serotonergic actions on these fibers. TMCs would thus be cellular interfaces mediating immune action in the nervous system in relation with the hormonal status of the organism. D 2004 Elsevier B.V. All rights reserved. Keywords: Thalamic mast cells; Median eminence; Sumatriptan; Ondansetron; Neuroendocrine process; Immunomodulation 1. Introduction Several studies have revealed the existence of mast cells in the mammalian central nervous system (Ibrahim, 1974; Dropp, 1976; Silver et al., 1996; Michaloudi and Papadopoulos, 1999; Servie `re et al., 2003). Mast cells are immunocompetent cells that can be identified by the metachromatic properties of their proteoglycan contents, mostly heparin, within specific secretory granules. Toluidine blue is the basic stain most commonly used to characterize them (Humason, 1972). In adult brain, the occurrence of mast cells has been limited to the diencephalon (thalamus, hypothalamus and epithalamus), leptomeninges and choroid plexus (Dropp, 1972; Kru ¨ger, 1974; Persinger, 1977; Zhuang et al., 1999). Mast cells are especially numerous in the thalamus. In rats their numbers have been shown to vary with age, sex and physiological state, as well as with environmental and hormonal factors (Persinger, 1980; Goldschmidt et al., 1984; Lafreniere and Persinger, 2001; Asarian et al., 2002). They are more numerous in females than in males and show a left-sided predominance, especially in females (Kru ¨ger, 1974; Goldschmidt et al., 1984; Michaloudi and Papadopoulos, 1999). Thalamic mast cells exhibit perivascular prevalence but in some instances can be found within the parenchyma surrounded by normal elements of the neuropil (Silver et al., 1996). There is some evidence that mast cell degranulation increases permeability of rat blood–brain barrier (Zhuang et al., 1996; Esposito et al., 2001). They have all the ultrastructure and biochemical characteristics of mature cells, and resemble connective tissue types (Pang et al., 1996). Mast cells can rapidly reach the brain via the blood supply, and this may account for the rapid increases in their number in response to altered physiological conditions (Silverman et al., 2000). Although the physiological functions of thalamic mast cells still remain unknown their privileged location within the thalamus including its nuclei sending cortical projections 0165-5728/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jneuroim.2004.08.020 * Corresponding author. Tel.: +33 1 42 86 22 82; fax: +33 1 49 27 90 62. E-mail address: david.dubayle@univ-paris5.fr (D. Dubayle). Journal of Neuroimmunology 159 (2005) 20 – 30 www.elsevier.com/locate/jneuroim