Altered cortical GABA neurotransmission in schizophrenia

Insights into novel therapeutic strategies

Ana D. Stan, David A. Lewis

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1557-1562
Number of pages6
JournalCurrent Pharmaceutical Biotechnology
Volume13
Issue number8
DOIs
StatePublished - Jun 2012

Fingerprint

Synaptic Transmission
gamma-Aminobutyric Acid
Schizophrenia
Neurons
GABA Plasma Membrane Transport Proteins
GABAergic Neurons
Membrane Transport Proteins
Pyramidal Cells
Presynaptic Terminals
GABA-A Receptors
Prefrontal Cortex
Therapeutics
Pharmacology
Brain
Axon Initial Segment

Keywords

  • Basket neuron
  • Chandelier neuron
  • GABA-A receptor
  • Parvalbumin
  • Prefrontal cortex

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Biotechnology

Cite this

Altered cortical GABA neurotransmission in schizophrenia : Insights into novel therapeutic strategies. / Stan, Ana D.; Lewis, David A.

In: Current Pharmaceutical Biotechnology, Vol. 13, No. 8, 06.2012, p. 1557-1562.

Research output: Contribution to journalArticle

@article{c1c5bc6fba6e4294a975ab9b55daddc4,
title = "Altered cortical GABA neurotransmission in schizophrenia: Insights into novel therapeutic strategies",
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 = "Basket neuron, Chandelier neuron, GABA-A receptor, Parvalbumin, Prefrontal cortex",
author = "Stan, {Ana D.} and Lewis, {David A.}",
year = "2012",
month = "6",
doi = "10.2174/138920112800784925",
language = "English (US)",
volume = "13",
pages = "1557--1562",
journal = "Current Pharmaceutical Biotechnology",
issn = "1389-2010",
publisher = "Bentham Science Publishers B.V.",
number = "8",

}

TY - JOUR

T1 - Altered cortical GABA neurotransmission in schizophrenia

T2 - Insights into novel therapeutic strategies

AU - Stan, Ana D.

AU - Lewis, David A.

PY - 2012/6

Y1 - 2012/6

N2 - 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.

AB - 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.

KW - Basket neuron

KW - Chandelier neuron

KW - GABA-A receptor

KW - Parvalbumin

KW - Prefrontal cortex

UR - http://www.scopus.com/inward/record.url?scp=84862605801&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862605801&partnerID=8YFLogxK

U2 - 10.2174/138920112800784925

DO - 10.2174/138920112800784925

M3 - Article

VL - 13

SP - 1557

EP - 1562

JO - Current Pharmaceutical Biotechnology

JF - Current Pharmaceutical Biotechnology

SN - 1389-2010

IS - 8

ER -