Serotonin of mast cell origin contributes to hippocampal function

Psychology Department, Columbia University, 406 Schermerhorn Hall, 1190 Amsterdam Ave., New York, NY 10027, USA.
European Journal of Neuroscience (Impact Factor: 3.18). 05/2012; 36(3):2347-59. DOI: 10.1111/j.1460-9568.2012.08138.x
Source: PubMed


In the central nervous system, serotonin, an important neurotransmitter and trophic factor, is synthesized by both mast cells and neurons. Mast cells, like other immune cells, are born in the bone marrow and migrate to many tissues. We show that they are resident in the mouse brain throughout development and adulthood. Measurements based on capillary electrophoresis with native fluorescence detection indicate that a significant contribution of serotonin to the hippocampal milieu is associated with mast cell activation. Compared with their littermates, mast cell-deficient C57BL/6 Kit(W-sh/W-sh) mice have profound deficits in hippocampus-dependent spatial learning and memory and in hippocampal neurogenesis. These deficits are associated with a reduction in cell proliferation and in immature neurons in the dentate gyrus, but not in the subventricular zone - a neurogenic niche lacking mast cells. Chronic treatment with fluoxetine, a selective serotonin reuptake inhibitor, reverses the deficit in hippocampal neurogenesis in mast cell-deficient mice. In summary, the present study demonstrates that mast cells are a source of serotonin, that mast cell-deficient C57BL/6 Kit(W-sh/W-sh) mice have disrupted hippocampus-dependent behavior and neurogenesis, and that elevating serotonin in these mice, by treatment with fluoxetine, reverses these deficits. We conclude that mast cells contribute to behavioral and physiological functions of the hippocampus and note that they play a physiological role in neuroimmune interactions, even in the absence of inflammatory responses.

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    • "N-cadherin or synaptic cell adhesion molecule (SynCAM) (Suzuki et al. 2004; Furuno et al. 2005). Mast cell-derived serotonin contributes to neurogenesis and to the behavioral and physiological function of the hippocampus (Nautiyal et al. 2012). Mast cell proteases, such as tryptase, signal nerves through PARs; PAR2 activation has been implicated in increased intestinal permeability and visceral hypersensitivity in rodents (Déry et al. 1998; Vergnolle et al. 2001; Coelho et al. 2002; Cenac et al. 2003). "
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