Decreased hippocampal expression of a glutamate receptor gene in schizophrenia

Harrison, Paul J.; McLaughlin, Daniel P.; Kerwin, Robert

doi:10.1016/0140-6736(91)93392-m

Cited by 229 publications

(83 citation statements)

References 22 publications

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“…Several investigators have reported that the expression of AMPA and kainate receptor subtypes is reduced in the hippocampus, an area that is thought to play an important role in schizophrenia (Gao et al, 2000;Meador-Woodruff & Healy, 2000). In a number of studies, the AMPA subunits GluR1 and GluR2 were decreased in the hippocampus and the parahippocampal gyrus (Eastwood et al, 1995b(Eastwood et al, , 1997a(Eastwood et al, , 1997bHarrison et al, 1991). In concordance, ligand binding to AMPA receptors was decreased (Kerwin et al, 1990).…”

Section: The Role Of Glutamate In Neurotoxicity-supporting

confidence: 48%

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

292

165

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The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system.

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Section: The Role Of Glutamate In Neurotoxicity-supporting

confidence: 48%

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

292

165

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“…The preponderance of these studies has detected complex and regionally specific alterations in ␣ -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate, and N-methyl-D-aspartate (NMDA) receptor expression, especially in cingulate cortex and medial temporal lobe structures (Akbarian et al 1996;Aparicio-Legarza et al 1998;Deakin et al 1989;Eastwood et al 1997aEastwood et al , 1997bEastwood et al , 1995Grimwood et al 1999;Harrison et al 1991;Healy et al 1998;Humphries et al 1996;Ibrahim et al 2000;Kerwin et al 1988Kerwin et al , 1990Kornhuber et al 1989; MeadorWoodruff and Healy 2000;Nishikawa et al 1983;Noga et al 1997;Ohnuma et al 1998;Porter et al 1997;Sokolov 1998). Recently, such studies have been extended to other brain regions associated with limbic circuitry felt to be disturbed in psychiatric illnesses, including the striatum.…”

Section: Because Abnormalities Of Glutamatergic Neurotransmission In mentioning

confidence: 99%

Striatal Excitatory Amino Acid Transporter Transcript Expression in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

McCullumsmith

Meador‐Woodruff

2002

Neuropsychopharmacology

178

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Because abnormalities of glutamatergic neurotransmission in psychiatric illness are likely not limited to glutamate receptor expression, we investigated expression of excitatory amino acid transporters (EAATs) in the striatum. The EAATs, normally expressed in both glia (EAAT1 and EAAT2) and neurons (EAAT3 and EAAT4), have previously been implicated in Huntington's disease, amyotrophic lateral sclerosis, and schizophrenia. In A growing literature suggests abnormal expression of ionotropic glutamate receptors in the brain in schizophrenia. The preponderance of these studies has detected complex and regionally specific alterations in ␣ -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate, and N-methyl-D-aspartate (NMDA) receptor expression, especially in cingulate cortex and medial temporal lobe structures (Akbarian et al. 1996;Aparicio-Legarza et al. 1998;Deakin et al. 1989;Eastwood et al. 1997aEastwood et al. , 1997bEastwood et al. , 1995Grimwood et al. 1999;Harrison et al. 1991;Healy et al. 1998;Humphries et al. 1996;Ibrahim et al. 2000;Kerwin et al. 1988Kerwin et al. , 1990Kornhuber et al. 1989; MeadorWoodruff and Healy 2000;Nishikawa et al. 1983;Noga et al. 1997;Ohnuma et al. 1998;Porter et al. 1997;Sokolov 1998). Recently, such studies have been extended to other brain regions associated with limbic circuitry felt to be disturbed in psychiatric illnesses, including the striatum. Increased NMDA receptor binding at both the glycine/D-serine coagonist site and the intrachannel MK801 site was detected in the putamen, and increased CNQX (an AMPA/kainate antagonist) binding was detected in the caudate in schizophrenia (Aparicio-Legarza et al. (Arriza et al. 1993;Utsunomiya-Tate et al. 1996). The transporters have specific patterns of cellular localization: EAAT1 and EAAT2 have been localized to astroglia, whereas EAAT3 and EAAT4 are localized to neurons (Bar-Peled et al. 1997;Chaudhry et al. 1995;Furuta et al. 1997;Lehre et al. 1995;Milton et al. 1997;Rothstein et al. 1994;Sims and Robinson 1999;Yamada et al. 1996Yamada et al. , 1997. The best studied of the glutamate transporters, EAAT2 (called GLT-1 in the rat) accounts for ‫ف‬ 90% of forebrain glutamate reuptake in the rodent (Rothstein et al. 1996;Tanaka et al. 1997). The predominately glial expression of EAAT2 mRNA and protein, observed throughout the human brain, is highest in the forebrain (Bar-Peled et al. 1997;Milton et al. 1997). Similar to EAAT2, EAAT3 (called EAAC1 in the rat) protein expression in the human brain is detected in the frontal cortex and the hippocampus (Bar-Peled et al. 1997). EAAT3 is localized to both post-and presynaptic neuronal soma and is associated with ‫ف‬ 40% of rodent hippocampal glutamate transport (Rothstein et al. 1994). In contrast, levels of EAAT1 (called GLAST in the rat) and EAAT4 protein expression in the rodent central nervous system (CNS) are highest in the cerebellum in the Bergmann glia and Purkinje cell types, respectively, whereas human studies of EAAT1 protein expression indicate high levels in the f...

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“…One intriguing finding is an impaired expression of glutamate receptors in the hippocampal areas where various structural/ pathological abnormalities in schizophrenic brain have been observed. [43][44][45][46] Levels of mRNAs for AMPA, kainate and NMDA glutamate receptor subunits are abnormal, and some of these changes have been confirmed at the protein level. 47 Reduction of transmitter receptors is not a generalized phenomenon in schizophrenia, however.…”

Section: Phenotypic Abnormalities In Brain Neuronsmentioning

confidence: 99%

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

2000

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Medical treatment with various cytokines can provoke psychiatric symptoms. Conversely, psychiatric patients can display abnormalities in cytokine and neurotrophic factor expression. Such observations have pointed to the potential contribution of cytokines and growth factors to schizophrenic pathology and/or etiology. The cellular targets of the relevant factors and the nature of their actions remain to be explored in mental illness, however. Recent physiological studies demonstrate that cytokines and neurotrophic factors can markedly influence synaptic transmission and plasticity upon acute or chronic application. Moreover, many of the molecular alterations observed in the schizophrenic brain are consistent with abnormalities in cytokine and neurotrophic factor regulation of these molecules. In this review, we summarize these molecular pathology findings for schizophrenia and highlight the neurodevelopmental activities of cytokines and neurotrophic factors that may contribute to the etiology or pathology of this illness. Molecular Psychiatry (2000) 5, 594-603.

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Decreased hippocampal expression of a glutamate receptor gene in schizophrenia

Cited by 229 publications

References 22 publications

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Striatal Excitatory Amino Acid Transporter Transcript Expression in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

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