Markers of glutamate and GABA neurotransmission in the prefrontal cortex of schizophrenia subjects: Disease effects differ across anatomical levels of resolution.
E/I balance
GABA
Glutamate
Layer 3
Prefrontal cortex
Schizophrenia
Journal
Schizophrenia research
ISSN: 1573-2509
Titre abrégé: Schizophr Res
Pays: Netherlands
ID NLM: 8804207
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
29
04
2019
revised:
04
06
2019
accepted:
07
06
2019
pubmed:
13
7
2019
medline:
22
6
2021
entrez:
13
7
2019
Statut:
ppublish
Résumé
Cognitive dysfunction in individuals with schizophrenia is thought to reflect, at least in part, altered levels of excitatory and inhibitory neurotransmission in the dorsolateral prefrontal cortex (DLPFC). Studies of the postmortem human brain allow for interrogation of the disease-related alterations in markers of excitatory and inhibitory neurotransmission at different levels of anatomical resolution. Here, we re-analyzed six published datasets from postmortem studies of schizophrenia to assess molecular markers of glutamate and GABA neurotransmission in the DLPFC at three levels of anatomical resolution: 1) total cortical gray matter, 2) gray matter restricted to layer 3, and 3) a layer 3 local circuit composed of excitatory pyramidal cells and inhibitory, parvalbumin-containing, GABA neurons. We formulated composite measures of glutamate and GABA neurotransmission from z-scores of key transcripts that regulate these functions. Relative to unaffected comparison subjects, the composite glutamate measure was higher in schizophrenia subjects in total gray matter homogenates but lower in samples restricted to layer 3 or the layer 3 local circuit. The composite index of GABA neurotransmission did not differ between subject groups in total gray matter homogenates but was lower in schizophrenia subjects in layer 3 and lower still in the local layer 3 circuit. These findings suggest that the balance of excitation and inhibition in the DLPFC of schizophrenia subjects differs depending on the level of anatomical resolution studied, highlighting the importance of layer- and cell type-specific studies to understand disease-related alterations in cortical circuitry.
Identifiants
pubmed: 31296415
pii: S0920-9964(19)30224-5
doi: 10.1016/j.schres.2019.06.003
pmc: PMC6946893
mid: NIHMS1534168
pii:
doi:
Substances chimiques
Glutamic Acid
3KX376GY7L
gamma-Aminobutyric Acid
56-12-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
86-94Subventions
Organisme : NIMH NIH HHS
ID : P50 MH103204
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH043784
Pays : United States
Organisme : NIMH NIH HHS
ID : R37 MH043784
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008208
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest David A. Lewis currently receives investigator-initiated research support from Pfizer and Merck. All other authors report no conflicts of interest.
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