Glutamate Signaling Pathways Research Articles

Immunohistochemical Localization of D-Aspartate in Islets of Langerhans

D-aspartate is a putative modulator of neuroendocrine functions, and is present in various neuroendocrine cells as well as the central nervous system. Here we show that the islet of Langerhans is a D-aspartate-containing endocrine organ. Immunohistochemical analysis with specific antibodies against D-aspartate indicated that D-aspartate is present in all islet cells, and predominantly present in alpha cells and a subpopulation of F-cells. Since these cells are glutamatergic in nature, it is possible that D-aspartate is involved in the glutamate signaling pathways in the islets.

Gene profiling links SCA1 pathophysiology to glutamate signaling in Purkinje cells of transgenic mice.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of a polyglutamine repeat within the disease protein, ataxin 1. To elucidate cellular pathways involved in SCA1, we used DNA microarrays to determine the pattern of gene expression in SCA1 transgenic mice at two specific times in the disease process; 5 weeks, a timepoint prior to onset of pathology, and 12 weeks, at the midpoint of the disease progression. Taking advantage of the availability of three SCA1 transgenic mouse lines, each expressing a different form of ataxin-1, we utilized a strategy that resulted in the identification of a limited number of genes with an altered pattern of expression specific to the development of disease. By comparing the pattern of gene expression in the SCA1 ataxic B05-ataxin-1[82Q] transgenic mouse line with those seen in two non-ataxic lines, A02-ataxin-1[30Q] and K772T-[82Q], nine genes were identified whose expression was consistently altered in the cerebellum of B05[82Q] mice at 5 and 12 weeks of age. Interestingly, five of the genes in this group form a biological cohort centered on glutamate signaling pathways in Purkinje cells.

Non-neuronal glutamate signalling pathways

It is becoming increasingly apparent that the role of glutamate receptors in signalling at synapses is not confined to the CNS, as once believed, and that they also function in several non-neuronal tissues. The aim of this review is to summarise current knowledge regarding peripheral glutamate signalling and discuss the role of glutamate as a more ubiquitous signalling agent. As one avenue for therapeutic intervention may be by manipulation of intercellular communication pathways, increased awareness and understanding of glutamate signalling will help in the design of treatment schedules for a range of biological disorders including skin disease, osteoporosis, blood clotting disorders and diabetes. These avenues have the possibility to advance rapidly into clinical practice because agents developed to modulate central glutamate receptor function could be targeted to new sites without the requirement for completely new drug discovery or clinical chemistry programmes.

Involvement of glutamate in transmission of afferent constrictive inputs from the airways to the nucleus tractus solitarius in ferrets

In this study, we identified the neurons within nucleus tractus solitarius (nTS) activated by stimulation of airway sensory systems and examined the expression of AMPA receptor subtype(s) by these cells. We also investigated the possible involvement of endogenously released glutamate and AMPA receptors in the transmission of excitatory inputs from the sensory system of the respiratory tract to the neurons of the nTS. In these experiments we used: (1) immunodetection of c-fos encoded protein (cFos) expression to identify the nTS neurons activated by the stimulation of the airway sensory system; (2) receptor immunochemistry and confocal microscopy to determine the receptor(s) expressed by activated nTS neurons; (3) microdialysis to measure glutamate release, and (4) physiological measurements to examine the effects of selective receptor blockers, and thereby define the role of the glutamate and AMPA glutamatergic receptor subtype(s) in reflexly induced airway constriction. The results showed that activation of airway sensory receptors, by inhalation of aerosolized histamine or capsaicin, induced cFos expression in a subset of nTS neurons that also expressed the AMPA subtype of glutamate receptors. Furthermore, activation of sensory bronchoconstrictive receptors induced glutamate release within nTS, and blockade of the AMPA receptor subtype within nTS inhibited reflexly increased cholinergic outflow to the airways. These data indicate for the first time that glutamate and AMPA receptor signaling pathways are involved in the transmission of afferent inputs from the airways to the nTS, and in mediating reflex airway constriction.

Stat3 participates in the metabotropic glutamate signaling pathway in Bergmann glial cells.

Purkinje cells establish a glutamatergic synapse with the parallel fibers in the cerebellum. Bergmann glial cells surround this synapse. The transcription factor Stat3, highly expressed in cerebellum, is present in cultures of chick Bergmann glia. Treatment of these cells with L-glutamate induces the tyrosine-phosphorylation of Stat3. The maximal phosphorylation was observed after 15 min and by 30 min returned to basal levels. This effect correlated with Stat3 translocation to nucleus and the appearance of a retarded band in gel mobility shift assays. The effects observed with L-glutamate were mediated through metabotropic glutamate receptors. These results further support the notion that glial cells respond to L-glutamate through changes in the existing proteins and also in gene expression regulation.

Expression of an N-Methyl-D-Aspartate-Type Receptor by Human and Rat Osteoblasts and Osteoclasts Suggests a Novel Glutamate Signaling Pathway in Bone

Signaling between the various types of cells found in bone is responsible for controlling the activity of osteoblasts and osteoclasts, and therefore the regulation of bone mass. Our identification of a neuronal glutamate transporter in osteoblasts and osteocytes suggests the possibility that bone cells may use the excitatory amino acid glutamate as a signaling molecule. In these studies we report the expression of different subtypes of glutamate receptors in osteoblasts and osteoclasts in vitro and in vivo. We have identified expression in human and rat bone cells of N-methyl-D-aspartate receptor-1 (NMDAR-1) and 2D subunits and PSD-95, the NMDA receptor clustering protein associated with signaling in the central nervous system. In situ hybridization and immunohistochemistry localized NMDAR-1 expression to osteoblasts and osteoclasts in human tissue sections. These findings strengthen the suggestion that glutamate is involved in signaling between bone cells.