Reduced GABA uptake sites in the temporal lobe in schizophrenia

Simpson, M.D.C.; Slater, P.; Deakin, Bill; Royston, M.C.; Skan, Wendy

doi:10.1016/0304-3940(89)90819-7

Cited by 187 publications

(93 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These studies showed reductions in the concentration of cortical GABA [6] and the activity of glutamate decarboxylase (GAD) [7], the enzyme that synthesizes GABA. These observations were confirmed and extended in subsequent studies showing alteration in several presynaptic components of the GABAergic system [8][9][10][11][12][13][14]. The GABA deficit does not affect all classes of cortical GABAergic interneurons equally [15], but is restricted mainly to the basket and chandelier type of interneurons [16,17].…”

Section: Gaba Hypofunctionsupporting

confidence: 66%

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

Lisman

Coyle

Green

et al. 2008

Trends in Neurosciences

913

824

View full text Add to dashboard Cite

Many risk genes interact synergistically to produce schizophrenia and many neurotransmitter interactions have been implicated. We have developed a circuit-based framework for understanding gene and neurotransmitter interactions. NMDAR hypofunction has been implicated in schizophrenia because NMDAR antagonists reproduce symptoms of the disease. One action of antagonists is to reduce the excitation of fast-spiking interneurons, resulting in disinhibition of pyramidal cells. Overactive pyramidal cells, notably those in the hippocampus, can drive a hyperdopaminergic state that produces psychosis. Additional aspects of interneuron function can be understood in this framework, as follows. (i) In animal models, NMDAR antagonists reduce parvalbumin and GAD67, as found in schizophrenia. These changes produce further disinhibition and can be viewed as the aberrant response of a homeostatic system having a faulty activity sensor (the NMDAR). (ii) Disinhibition decreases the power of gamma oscillation and might thereby produce negative and cognitive symptoms. (iii) Nicotine enhances the output of interneurons, and might thereby contribute to its therapeutic effect in schizophrenia.

show abstract

Section: Gaba Hypofunctionsupporting

confidence: 66%

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

Lisman

Coyle

Green

et al. 2008

Trends in Neurosciences

913

824

View full text Add to dashboard Cite

show abstract

“…More consistent findings have come from studies of the GABA uptake site where reductions of this marker have been consistently observed in prefrontal cortex (Simpson et al 1989), amygdala (Reynolds 1983), and hippocampus (Reynolds et al 1990) of schizophrenic brain. A recent attempt to replicate this finding in prefrontal and temporal cortex, however, did not show any differences in schizophrenics (Simpson et al 1998).…”

Section: Postmortem Evidence For a Gaba Defect In Schizophreniamentioning

confidence: 63%

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

Beneš

Berretta

2001

Neuropsychopharmacology

990

643

View full text Add to dashboard Cite

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 ...

show abstract

“…Examination of brain regions implicated in schizophrenia has revealed a reduction of GABAergic axon terminals in the hippocampus 109,110 as well as the temMolecular Psychiatry poral 110 and prefrontal cortex. 111 Neurochemical and in situ hybridization studies in the frontal and temporal cortex indicate that the enzyme responsible for synthesizing GABA, GAD, is also reduced in schizophrenia.…”

Section: Abnormalities In Neurotransmitter Systemsmentioning

confidence: 99%

“…117 Similarly, several populations of peptidergic interneurons (which are predominately inhibitory) appear to be impaired in temporal and frontal cortices, hippocampus, or in other limbic structures. [118][119][120][121][122][123] Although some of the foregoing studies have not been replicated or have produced inconsistent results, 110,124 the bulk of the evidence indicates that several types of local inhibitory neurotransmitter circuits are hypofunctional in corticohippocampal brain regions of schizophrenia patients. 91,100 Investigations of excitatory neurotransmitters in schizophrenia have produced a confusing and discrepant body of data.…”

Section: Abnormalities In Neurotransmitter Systemsmentioning

confidence: 99%

Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms

Pearce

2001

Mol Psychiatry

135

View full text Add to dashboard Cite

The task of defining schizophrenia pathogenesis has fascinated and frustrated researchers for nearly a century. In recent years, unprecedented advances from diverse fields of study have given credence to both viral and developmental theories. This review considers possible mechanisms by which viral and developmental processes may interact to engender schizophrenia. Many of the current controversies in schizophrenia pathogenesis are reviewed in light of the viral hypothesis, including: epidemiological findings and the role of a genetic diathesis, phenotype heterogeneity, abnormalities in excitatory and inhibitory neurotransmitter systems, anomalous cerebral latereralization, and static vs progressive disease. The importance of animal models in elucidating the impact of viral infections on developing neurons is illustrated by recent studies in which neonatal rats are infected with lymphocytic choriomeningitis virus in order to examine alterations in hippocampal circuitry. Finally, consideration is given to a new hypothesis that some cases of schizophrenia could be instigated by a viral infection that disrupts developing inhibitory circuits, consequently unleashing glutamatergic neurotransmission leading to selective excitotoxicity, and a degenerative disease course. Molecular Psychiatry (2001) 6, 634-646.

show abstract

Reduced GABA uptake sites in the temporal lobe in schizophrenia

Cited by 187 publications

References 19 publications

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms

Contact Info

Product

Resources

About