http://precedings.nature.com/tags/glutamate Recently posted documents tagged with 'glutamate' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://dx.doi.org/10.1038/npre.2008.2330.1 Many scientific efforts have been well done to investigate the effects of anti inflammatory agents on the degenerative brain diseases such as Parkinson’s (PD) or Alzheimer’s disease and their affiliated sings. Previously we showed the effectiveness of steroids on rigidity of PD and in the study for further mechanistic investigation of that observation the microdialysis technique was employed to determine the striatal dopamine changes in parkinsonian rats after administration of betamethasone (0.12, 0.24 mg/kg) respectively. Our findings showed us the significant increase in the striatal dopaminergic neurotransmission (P http://dx.doi.org/10.1038/npre.2008.2330.1 Fri, 26 Sep 2008 09:13:00 UTC Steroidal anti inflammatory drug betamethasone significantly alters level of striatal dopamine in a rat model of Parkinson’s disease doi:10.1038/npre.2008.2330.1 2008-09-26 Mehdi Shafiee Ardestani Nature Precedings 2008-09-26T09:13:00Z Manuscript Chemistry Immunology Neuroscience Pharmacology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1767/version/1 Negative feedback can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. At the Drosophila neuromuscular junction, a mutation in the type II metabotropic glutamate receptor gene (mGluRA) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. We show that mGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in an mGluRA-dependent manner. In humans, PI3K and type II mGluRs are implicated in epilepsy, neurofibromatosis, autism, schizophrenia and other neurological disorders; however, neither the link between type II mGluRs and PI3K, nor the role of Foxo in the control of neuronal excitability, had been previously reported. Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability. http://precedings.nature.com/documents/1767/version/1 Mon, 07 Apr 2008 10:42:18 UTC A PI3K-mediated negative feedback regulates Drosophila motor neuron excitability hdl:10101/npre.2008.1767.1 2009-01-09 Eric Howlett Nature Precedings 2008-04-07T10:42:18Z Manuscript Molecular Cell Biology Neuroscience http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2006.9.1 Integration of neurotransmitter and neuromodulator signals in the striatum plays a central role in the functions and dysfunctions of the basal ganglia. DARPP-32 is a key actor of this integration in the GABAergic medium-size spiny neurons, in particular in response to dopamine and glutamate. When phosphorylated by cAMP-dependent protein kinase (PKA) DARPP-32 inhibits protein phosphatase-1 (PP1), whereas when phosphorylated by cyclin-dependent kinase 5 (CDK5) it inhibits PKA. DARPP-32 is also regulated by casein kinases and by several protein phosphatases. These complex and intricate regulations make simple predictions of DARPP-32 dynamic behaviour virtually impossible. We used detailed quantitative modelling of the regulation of DARPP-32 phosphorylation to improve our understanding of its function. The models included all the combinations of the three best characterized phosphorylation sites of DARPP-32, their regulation by kinases and phosphatases, and the regulation of those enzymes by cAMP and Ca2+ signals. Dynamic simulations allowed to observe the temporal relationships between cAMP and Ca2+ signals. We confirmed that the proposed regulation of protein phosphatase-2A (PP2A) by calcium can account for the observed decrease of Threonine 75 phosphorylation upon glutamate receptor activation. Sensitivity analysis showed that CDK5 activity is a major regulator of the response, as previously suggested. Conversely, the regulation of PP2A by PKA or by calcium, had little effect on the function of DARPP-32 in these conditions. The simulations showed that DARPP-32 is not only a robust signal integrator, but also a coincidence detector, the delay between cAMP and calcium signals affecting the response to the latter. This integration did not depend on the concentration of DARPP-32, while the absolute response on PP1 varied linearly. In silico mutants showed that Ser137 phosphorylation affects the coincidence detector function, and that constitutive phosphorylation in Ser137 transforms DARPP-32 in a quasi-irreversible switch. This work is a first attempt to better understand the complex interactions between cAMP and Ca2+ regulation of DARPP-32. Progressive inclusion of additional components should lead to a realistic model of signalling networks underlying the function of striatal neurons. http://dx.doi.org/10.1038/npre.2006.9.1 Thu, 30 Nov 2006 15:06:03 UTC DARPP-32 is a robust integrator of dopamine and glutamate signals doi:10.1038/npre.2006.9.1 2006-11-30 Nicolas Le Novere Nature Precedings 2006-11-30T15:06:03Z Poster Neuroscience http://creativecommons.org/licenses/by/2.5/