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Current Pharmaceutical Biotechnology
ISSN (Print): 1389-2010
ISSN (Online): 1873-4316
VOLUME: 13
ISSUE: 8
DOI: 10.2174/138920112800784925      Price:  $58









Altered Cortical GABA Neurotransmission in Schizophrenia: Insights into Novel Therapeutic Strategies

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Author(s): Ana D. Stan and David A. Lewis
Pages 1557-1562 (6)
Abstract:
Altered markers of cortical GABA neurotransmission are among the most consistently observed abnormalities in postmortem studies of schizophrenia. The altered markers are particularly evident between the chandelier class of GABA neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons. For example, in the dorsolateral prefrontal cortex of subjects with schizophrenia immunoreactivity for the GABA membrane transporter is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. Both of these molecular changes appear to be compensatory responses to a presynaptic deficit in GABA synthesis, and thus could represent targets for novel therapeutic strategies intended to augment the brain’s own compensatory mechanisms. Recent findings that GABA inputs from neocortical chandelier neurons can be powerfully excitatory provide new ideas about the role of these neurons in the pathophysiology of cortical dysfunction in schizophrenia, and consequently in the design of pharmacological interventions.
Keywords:
Chandelier neuron, basket neuron, parvalbumin, GABA-A receptor, prefrontal cortex, "axon terminals", "GABA synthesis", novel therapeutic strategies
Affiliation:
Department of Psychiatry, University of Pittsburgh, 3811 O’Hara Street, W1651 BST, Pittsburgh, PA 15213, USA.