Glutamate hypothesis

Ishimaru, M, Kurumaji, A and Toru, M (1994) Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics evidence for glutamate hypothesis. Biol. Psychiat. 35 84-95. 

Greene JG, Greenamyre JT (1995) Characterization of the excitotoxic potential of the reversible succinate dehydrogenase inhibitor malonate. J Neurochem 64 430-436 Gunne LM, Andren PE (1993) An animal model for coexisting tardive dyskinesia and tardive parkinsonism—a glutamate hypothesis for tardive dyskinesia. Clin Neuropharmacol 16 90-95... 

Glutamatergic abnormalities are also a major feature of schizophrenia. They may actually cause the dopaminergic abnormalities in that disorder and then be exacerbated by them (Laruelle et al., 2005). The glutamate hypothesis simply states that NMDAR hypofunction contributes to the pathophysiology of schizophrenia (Coyle, 2006 Lindsley et al., 2006). A variant of this is the NMDA synaptic deficit hypothesis of MacDonald and Chafee (2006), which posits that each risk factor for schizophrenia impacts the NMDA glutamate synapse such that the cumulative effect drives NMDA synaptic function below a threshold for normal function. Supporting either form of the glutamate hypothesis is evidence that... 

One of the most popular hypotheses to explain schizophrenia, the glutamate hypothesis of schizophrenia, is based on the observation of psychotomimetic effects of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP), dizocilpine (MK-801), and ketamine. Like amphetamine, NMDA antagonists produce a psychosis-like state when administered to healthy individuals. Further... 

Blatt GJ, Yip J, Soghomonian J-J, Whitney E, Thevarkunnel S, Bauman ML, Kemper TL (2007) An emerging GABA/glutamate hypothesis of cerebellar dysfunction in autism. Int Meet Autism Res 6 144. 

In subsequent experiments (66), this locked substrate was used to obtain evidence for the hypothesis (67) that enzyme-bound y-glutamyl phosphate 14 is an intermediate in the enzyme-catalyzed reaction. All attempts to isolate this acyl phosphate 14 have failed (66), presumably because of the marked tendency of this intermediate to cyclize to pyrrolidonecarboxyUc acid, 15, and to hydrolyze to glutamic acid. 

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