Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A capillary column gas-liquid chromatography selected ion monitoring-based method was developed for the measurement of [13C,15N]N-methyltryptamine ( NMT ) in human urine. The method was employed to establish the extent of conversion of [13C,15N]tryptamine to the correspondingly labeled NMT in schizophrenic patients in an attempt to demonstrate whether methylation of tryptamine plays a role in schizophrenia. Mass spectrometric detection in the assay procedure is via chemical ionization (Isobutane) with monitoring of the MH+ ions of the trimethylsilyl derivatives of [13C,15N] NMT and the internal standard, [2H3,13C,15N] NMT . The assay possesses a sensitivity limit (using 200 ml of urine) of ca. 0.1 ng/ml, corresponding to substrate conversion of ca. 0.00005% with a 75 mg dose (i.v.) of labeled tryptamine. Evidence for methylation was found with only one of seven patients studied; the extent of substrate conversion for the one individual was only 0.0001%. These results do not support the indoleamine--methylation hypothesis of schizophrenia.
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PMID:Capillary column gas-liquid chromatography selected ion monitoring assay for [13C, 15N]N-methyltryptamine in human urine: failure to detect conversion of [13C,15N]tryptamine in schizophrenia patients. 673 54

Abnormal synaptic plasticity has been implicated in the cognitive deficits seen in schizophrenia, where alterations have been found in neurotransmission, signaling and dendritic dynamics. Rapid rearrangement of the actin cytoskeleton is critical for plasticity and abnormalities of molecular regulators of this process are candidates for understanding mechanisms underlying these changes in schizophrenia. The myristoylated, alanine-rich C-kinase substrate (MARCKS) is crucial for many roles associated with synaptic plasticity, including facilitation of neurotransmission, dendritic branching and in turn cognitive function. Accordingly, we hypothesized that this protein is abnormally expressed or regulated in schizophrenia. We measured protein expression of MARCKS by Western blot analysis in postmortem samples of dorsolateral prefrontal cortex (DLPFC) from elderly schizophrenia patients (N=16) and a comparison group (N=20). We also assayed phosphorylated-MARCKS (pMARCKS), given the role of phosphorylation in reversing membrane association by MARCKS. We found decreased expression of both MARCKS and pMARCKS in schizophrenia. Altered myristoylation may be a mechanism that explains this down-regulation of MARCKS, so we also assayed expression of the two isoforms of the key myristoylation enzyme, NMT, and an enzymatic inhibitor of this enzyme, NMT-inhibitor protein (NIP71) by Western blotting in these same subjects. Expression did not change between groups for these proteins, suggesting a mechanism other than myristoylation is responsible for decreased MARCKS expression in schizophrenia. These data suggest a potential mechanism underlying aspects of altered synaptic plasticity observed in schizophrenia.
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PMID:Alterations of the myristoylated, alanine-rich C kinase substrate (MARCKS) in prefrontal cortex in schizophrenia. 2456 64