Current Pharmaceutical Biotechnology

Zeno Foldes-Papp
Visiting Professor of Medical Biochemistry
HELIOS Clinical Center of Emergency Medicine
Department for Internal Medicine
Alte-Koelner-Strasse 9
D-51688 Koeln-Wipperfuerth


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

Author(s): Ana D. Stan and David A. Lewis

Affiliation: Department of Psychiatry, University of Pittsburgh, 3811 O’Hara Street, W1651 BST, Pittsburgh, PA 15213, USA.

Keywords: Chandelier neuron, basket neuron, parvalbumin, GABA-A receptor, prefrontal cortex, "axon terminals", "GABA synthesis", novel therapeutic strategies


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.

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Article Details

Page: [1557 - 1562]
Pages: 6
DOI: 10.2174/138920112800784925