[3H]Muscimol binding sites increased in autopsied brains of chronic schizophrenics

Hanada, Susumu; Mita, Tatsuo; Nishino, Norikazu; Tanaka, Chikako

doi:10.1016/0024-3205(87)90341-9

Cited by 138 publications

(62 citation statements)

References 22 publications

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“…Previous studies also reported increased muscimol binding in the DLPFC of schizophrenia subjects that was most prominent in pyramidal neuron cell bodies. 19,20 However, because muscimol recognizes GABA binding sites in all types of GABA A receptors, decreased expression of some GABA A receptor subunits could be masked by increased expression of other subunits. Indeed, an upregulation of a2 subunit immunoreactivity in the axon initial segment of pyramidal neurons 21 and increased a2 mRNA expression in pyramidal neurons 71 were observed in the DLPFC of subjects with schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

“…For example, increased muscimolbinding in pyramidal neuron cell bodies 19,20 and increased GABA A receptor a2 subunits in the axon initial segments of pyramidal neurons 21 might represent compensatory receptor upregulation in response to decreased GABA release from GABA neurons, especially those that express PV. 4 However, the reports of decreased mRNA levels for the GABA A receptor g2 and d subunits 22,23 suggest that the downregulation of GABA A receptors containing these subunits might also contribute to disturbances in DLPFC inhibitory circuitry in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia

et al. 2007

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In subjects with schizophrenia, impairments in working memory are associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction appears to be due, at least in part, to abnormalities in c-aminobutyric acid (GABA)-mediated inhibitory circuitry. To test the hypothesis that altered GABA-mediated circuitry in the DLPFC of subjects with schizophrenia reflects expression changes of genes that encode selective presynaptic and postsynaptic components of GABA neurotransmission, we conducted a systematic expression analysis of GABA-related transcripts in the DLPFC of 14 pairs of schizophrenia and age-, sex-and post-mortem interval-matched control subjects using a customized DNA microarray with enhanced sensitivity and specificity. Subjects with schizophrenia exhibited expression deficits in GABA-related transcripts encoding (1) presynaptic regulators of GABA neurotransmission (67 kDa isoform of glutamic acid decarboxylase (GAD 67 ) and GABA transporter 1), (2) neuropeptides (somatostatin (SST), neuropeptide Y (NPY) and cholecystokinin (CCK)) and (3) GABA A receptor subunits (a1, a4, b3, c2 and d). Real-time qPCR and/or in situ hybridization confirmed the deficits for six representative transcripts tested in the same pairs and in an extended cohort, respectively. In contrast, GAD 67 , SST and a1 subunit mRNA levels, as assessed by in situ hybridization, were not altered in the DLPFC of monkeys chronically exposed to antipsychotic medications. These findings suggest that schizophrenia is associated with alterations in inhibitory inputs from SST/NPY-containing and CCKcontaining subpopulations of GABA neurons and in the signaling via certain GABA A receptors that mediate synaptic (phasic) or extrasynaptic (tonic) inhibition. In concert with previous findings, these data suggest that working memory dysfunction in schizophrenia is mediated by altered GABA neurotransmission in certain DLPFC microcircuits.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia

et al. 2007

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“…Contemporaneously, another study reported that the activity of GAD was significantly reduced in schizophrenics (Bird et al 1977). Although it began to appear that a pattern of decreased GABAergic activity was emerging, subsequent studies failed to show changes in either GABA levels or GAD activity (Cross et al 1979), even though one study did show a non-significant decrease of GAD in the prefrontal cortex (Hanada et al 1987). Because subjects who died suddenly were less apt to show such changes, it appeared that decreases in the specific activity of GAD might be related to the agonal state and might have been confounded in these studies (Bird 1977.…”

Section: Postmortem Evidence For a Gaba Defect In Schizophreniamentioning

confidence: 99%

“…The GABA agonist binding of [ 3 H]muscimol, was evaluated in the prefrontal cortex of controls and schizophrenics matched for age, but with an average postmortem interval of 8 and 13 hrs, respectively (Hanada et al 1987). The data indicated that the schizophrenics showed a 48% increase in the B max , but no difference in affinity for [ 3 H]muscimol binding.…”

Section: Postmortem Evidence For a Gaba Defect In Schizophreniamentioning

confidence: 99%

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

Beneš

Berretta

2001

Neuropsychopharmacology

996

643

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Neurons that express the compound, ␥ -aminobutyric acid (GABA), are broadly present throughout the central nervous system, although telencephalic structures, such as the cerebral cortex, show the most abundant quantities of this neurotransmitter (Jones 1987). In the discussion that follows, the anatomy and physiology of various types of GABAergic interneurons in the cortex and hippocampus will be discussed and related to recent postmortem studies implicating this transmitter system in the pathophysiology of schizophrenia and bi- 25 , NO . 1 polar disorder and their treatment with neuroleptic drugs (for more comprehensive reviews on cortical and hippocampal neurons see: Hof et al. 1993;Freund and Buzsaki 1996;Somogyi et al. 1998). NEUROBIOLOGY OF GABAERGIC INTERNEURONSBased on Golgi-impregnation studies, Ramon y Cajal provided the first descriptions of several different morphological subtypes of interneurons in the cerebral cortex and hippocampus (Ramon y Cajal 1893, 1911. In more recent years, it has been shown that, with some overlap, different morphological subtypes also have distinct distributions, connectivity, neurochemistry, and electrophysiological properties (for reviews see Hof et al. 1993;Freund and Buzsaki 1996). It is interesting to note that every segment of a pyramidal neuron, such as the soma, dendritic branches and spines, and the initial axonal segment, receives dense GABAergic synaptic innervation (O'Kusky and Colonnier 1982;Hendry et al. 1983;Houser et al. 1983; Beaulieu et al. 1992; for reviews see Jones 1993;Freund and Buzsaki 1996). Even more interestingly, each of these segments appears to be innervated by distinct GABAergic neuronal subtypes (see below).These differences strongly suggest that each of these subtypes plays a fundamentally different role in physiological and pathological mechanisms. In the discussion that follows, cortical interneurons will be described first, since our most basic understanding of GABAergic cells is derived from these populations. In more recent years, however, similar characterizations of interneurons in hippocampus have emerged. Although these cells show some striking similarities to their cortical counterparts, there are also some unique features that distinguish them. For this reason, interneurons in the hippocampus are discussed separately. Cortex Neuroanatomical Studies of Cortical Interneurons.Various types of GABAergic neurons can be categorized according to the type of synaptic profiles they are associated with, as this has direct implications for understanding the physiological role of these cells in cortical circuits. These categories are discussed below.A XO -S OMATIC I NHIBITORY S YNAPSES (B ASKET C ELLS ). The most commonly encountered interneurons ( Figure 1A) are multipolar in shape, i.e., they may have three or more primary dendritic branches emanating from their cell bodies, some having somata that are as large as those of pyramidal neurons (Jones and Hendry 1984). Using immunocytochemistry to localize the enzyme ). These cells also ...

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“…In the cingulate and frontal cortex, for instance, GABA-A receptor expression is somewhat elevated in schizophrenia. [48][49][50] Some of the findings from schizophrenic brain are controversial, and in some cases treatment of patients with neuroleptic drugs may confound the results. 51 …”

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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[3H]Muscimol binding sites increased in autopsied brains of chronic schizophrenics

Cited by 138 publications

References 22 publications

Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia

Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

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

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