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Assessing Glutamatergic Function and Dysfunction in Peripheral Tissues

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Glutamate is the major mediator of excitatory signaling in the mammalian central nervous system (CNS) and it has recently been described to have a central role in the transduction of sensory input in the peripheral nervous system (PNS), too. However, functional glutamatergic systems are expressed by peripheral non-neural tissues as well, such as heart, kidney, lungs, ovary, testis, blood and skin. Interestingly, glutamatergic alterations have been repeatedly described in these tissues in various neuropsychiatric diseases. Here we will review evidence suggesting that glutamate measurements obtained from sampling ex vivo peripheral cells can permit the assessment of the dynamics of glutamate release, uptake, receptor-mediated signaling, synthesis and degradation, and mirror homologous dysfunctions operative within the CNS in each single patient. Among all the available cell types we will focus on leukocytes, platelets and fibroblasts that can be easily obtained from patients multiple times without concerns related to post-mortem changes. Finally, we will briefly review another possibility, offered by testing plasma (and CSF) glutamate levels, allowing the indirect investigation of glutamatemediated crosstalk between central and peripheral compartments. Technical pitfalls of these biomarkers will be contextually emphasized.

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Keywords: Cerebrospinal fluid; fibroblasts; glutamate; glutamatergic alterations; leukocytes; neurotransmitter; peripheral markers; plasma; platelets; receptor-mediated signaling

Document Type: Research Article

Publication date: 01 March 2012

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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