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Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex

[Image: see text] Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We disc...

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Autores principales: Graham, Devon L., Durai, Heather H., Garden, Jamie D., Cohen, Evan L., Echevarria, Franklin D., Stanwood, Gregg D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372074/
https://www.ncbi.nlm.nih.gov/pubmed/25393953
http://dx.doi.org/10.1021/cn500235m
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author Graham, Devon L.
Durai, Heather H.
Garden, Jamie D.
Cohen, Evan L.
Echevarria, Franklin D.
Stanwood, Gregg D.
author_facet Graham, Devon L.
Durai, Heather H.
Garden, Jamie D.
Cohen, Evan L.
Echevarria, Franklin D.
Stanwood, Gregg D.
author_sort Graham, Devon L.
collection PubMed
description [Image: see text] Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders.
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spelling pubmed-43720742015-11-13 Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex Graham, Devon L. Durai, Heather H. Garden, Jamie D. Cohen, Evan L. Echevarria, Franklin D. Stanwood, Gregg D. ACS Chem Neurosci [Image: see text] Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders. American Chemical Society 2014-11-13 /pmc/articles/PMC4372074/ /pubmed/25393953 http://dx.doi.org/10.1021/cn500235m Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Graham, Devon L.
Durai, Heather H.
Garden, Jamie D.
Cohen, Evan L.
Echevarria, Franklin D.
Stanwood, Gregg D.
Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex
title Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex
title_full Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex
title_fullStr Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex
title_full_unstemmed Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex
title_short Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex
title_sort loss of dopamine d2 receptors increases parvalbumin-positive interneurons in the anterior cingulate cortex
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372074/
https://www.ncbi.nlm.nih.gov/pubmed/25393953
http://dx.doi.org/10.1021/cn500235m
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