BACKGROUND: The central role that the thalamus plays in information processing and sensory integration suggests that its dysfunction may be a factor in the pathophysiology of schizophrenia. Glutamate is a key neurotransmitter in thalamic function, and although all aspects of thalamic glutamate neurotransmission have not been elucidated, transcripts encoding members of each family of the glutamate receptors have been identified in the thalamus. Recently, activation of group II metabotropic glutamate receptors (mGluRs) was demonstrated in rats to ameliorate the behavioral effects associated with exposure to phencyclidine, an uncompetitive NMDA receptor antagonist that can induce psychotic symptoms, suggesting the possibility of mGluR abnormalities in schizophrenia. We investigated whether expression of thalamic mGluR mRNA is altered in this illness. METHODS: We examined the expression of the transcripts encoding the mGluR1, 2, 3, 4, 5, 7, and 8 receptors in postmortem thalamic tissue samples from elderly schizophrenic and control subjects, using in situ hybridization. We identified six thalamic nuclei in each section (anterior, dorsomedial, lateral dorsal, central medial, reticular, and nuclei of the ventral tier). RESULTS: There were no differences between elderly schizophrenic and control subjects in the expression of mGluR1, 2, 3, 4, 5, 7, or 8 transcript levels in any of these six thalamic nuclei. CONCLUSIONS: mGluR mRNA expression is not abnormal in the thalamus of patients with schizophrenia. The modulatory roles proposed for mGluRs, and the potentially important relationship between mGluRs and NMDA receptors, suggest that mGluRs may be involved in the pathophysiology of schizophrenia, but this is not detectable at this level of gene expression.
BACKGROUND: The central role that the thalamus plays in information processing and sensory integration suggests that its dysfunction may be a factor in the pathophysiology of schizophrenia. Glutamate is a key neurotransmitter in thalamic function, and although all aspects of thalamic glutamate neurotransmission have not been elucidated, transcripts encoding members of each family of the glutamate receptors have been identified in the thalamus. Recently, activation of group II metabotropic glutamate receptors (mGluRs) was demonstrated in rats to ameliorate the behavioral effects associated with exposure to phencyclidine, an uncompetitive NMDA receptor antagonist that can induce psychotic symptoms, suggesting the possibility of mGluR abnormalities in schizophrenia. We investigated whether expression of thalamic mGluR mRNA is altered in this illness. METHODS: We examined the expression of the transcripts encoding the mGluR1, 2, 3, 4, 5, 7, and 8 receptors in postmortem thalamic tissue samples from elderly schizophrenic and control subjects, using in situ hybridization. We identified six thalamic nuclei in each section (anterior, dorsomedial, lateral dorsal, central medial, reticular, and nuclei of the ventral tier). RESULTS: There were no differences between elderly schizophrenic and control subjects in the expression of mGluR1, 2, 3, 4, 5, 7, or 8 transcript levels in any of these six thalamic nuclei. CONCLUSIONS: mGluR mRNA expression is not abnormal in the thalamus of patients with schizophrenia. The modulatory roles proposed for mGluRs, and the potentially important relationship between mGluRs and NMDA receptors, suggest that mGluRs may be involved in the pathophysiology of schizophrenia, but this is not detectable at this level of gene expression.
Authors: John H Krystal; Sanjay J Mathew; D Cyril D'Souza; Amir Garakani; Handan Gunduz-Bruce; Dennis S Charney Journal: CNS Drugs Date: 2010-08 Impact factor: 5.749