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

作者：Stan Ana D; Lewis David A^*

来源：Current Pharmaceutical Biotechnology, 2012, 13(8): 1557-1562.

DOI：10.2174/138920112800784925

• Chandelier neuron
• basket neuron
• parvalbumin
• GABA-A receptor
• prefrontal cortex

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 GABA(A) receptor alpha 2 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.

• 出版日期2012-6