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- Title
GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon.
- Authors
Guidotti, Alessandro; Auta, James; Davis, John M; Dong, Erbo; Grayson, Dennis R; Veldic, Marin; Zhang, Xianquan; Costa, Erminio
- Abstract
Cortical gamma-aminobutyric acid (GABA)ergic neurons contribute to the orchestration of pyramidal neuron population firing as follows: (1) by releasing GABA on GABA(A) and GABA(B) receptors, (2) by releasing reelin in the proximity of integrin receptors located on cortical pyramidal neuron dendritic spines, and (3) through reelin contributing to the regulation of dendritic spine plasticity by modulating dendritic resident mRNA translation. In schizophrenia (SZ) and bipolar (BP) postmortem brains, the downregulation of mRNAs encoding glutamic acid decarboxylase 67 (GAD(67)) and reelin decreases the cognate proteins coexpressed in prefrontal cortex (PFC) GABAergic neurons. This finding has been replicated in several laboratories. Such downregulation suggests that the neuropil hypoplasticity found in the PFC of SZ and BP disorder patients may depend on a downregulation of GABAergic function, which is associated with a decrease in reelin secretion from GABAergic neuron axon terminals on dendrites, somata, or axon initial segments of pyramidal neurons. Indirectly, this GABAergic neuron downregulation may play a key role in the expression of positive and negative symptoms of SZ and BP disorders.
- Publication
Psychopharmacology, 2005, Vol 180, Issue 2, p191
- ISSN
0033-3158
- Publication type
Journal Article
- DOI
10.1007/s00213-005-2212-8