d-Serine administration provokes lipid oxidation and decreases the antioxidant defenses in rat striatum.
ABSTRACT The present work investigated the effects of intrastriatal administration of d-serine on relevant parameters of oxidative stress in striatum of young rats. d-Serine significantly induced lipid peroxidation, reflected by the significant increase of thiobarbituric acid-reactive substances, and significantly diminished the striatum antioxidant defenses, as verified by a decrease of the levels of reduced glutathione and total antioxidant status. Finally, d-serine inhibited superoxide dismutase activity, without altering the activities of glutathione peroxidase and catalase. In contrast, this d-amino acid did not alter sulfhydryl oxidation, a measure of protein oxidative damage. The present data indicate that d-serine in vivo administration induces lipid oxidative damage and decreases the antioxidant defenses in the striatum of young rats. Therefore, it is presumed that this oxidative stress may be a pathomechanism involved at least in part in the neurological damage found in patients affected by disorders in which d-serine metabolism is compromised, leading to altered concentrations of this d-amino acid.
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ABSTRACT: Mefenamic acid, a non-steroidal antiinflammatory drug (NSAID), directly and dose-dependently exhibits neuroprotective activity. In our study, we investigated the effects of mefenamic acid against d-serine on oxidative stress in the hippocampus, cortex and cerebellum of rats. Furthermore, the potential inflammatory and apoptotic effects of d-serine and potential protective effect of mefenamic acid were determined at mRNA and protein levels of TNF-α, IL-1β, Bcl-2 and Bax. We found that d-serine significantly increased oxidative stress, levels of inflammation- and apoptosis-related molecules in a region specific manner. Mefenamic acid treatment provided significant protection against the elevation of lipid peroxidation, protein oxidation, levels of TNF-α, IL-1β and Bax. As a conclusion, we suggest that d-serine, as a potential neurodegenerative agent, may have a pivotal role in the regulation of oxidative stress, inflammation and apoptosis; and NSAIDs, such as mefenamic acid, may assist other therapeutics in treating disorders where d-serine-induced neurotoxic mechanisms are involved in.Free Radical Research 02/2012; 46(6):726-39. · 3.28 Impact Factor
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ABSTRACT: Recently, D-serine has been identified as an important NMDA-receptor co-agonist, which might play a role in central nervous system development. We investigated this by studying rat P19 cells, an established model for neuronal and glial differentiation. Our results show that (1) the D-serine synthesizing enzyme serine racemase was expressed upon differentiation, (2) extracellular D-serine concentrations increased upon differentiation, which was inhibited by serine racemase antagonism, and (3) inhibition of D-serine synthesis or prevention of D-serine binding to the NMDA-receptor increased synaptophysin expression and intercellular connections, supporting a role for NMDA-receptor activation by D-serine, synthesized by serine racemase, in shaping synaptogenesis and neuronal circuitry during central nervous system development. In conjunction with recent evidence from literature, we therefore suggest that D-serine deficiency might be responsible for the severe neurological phenotype seen in patients with serine deficiency disorders. In addition, this may provide a pathophysiological mechanism for a role of D-serine deficiency in psychiatric disorders.JIMD reports. 01/2012; 6:47-53.
Article: Reference center spina bifidaAnnals of Physical and Rehabilitation Medicine. 01/2011; 54.