Subcortical dopaminergic deficits in a DISC1 mutant model: A study in direct reference to human molecular brain imaging

Hanna Jaaro-Peled, Minae Niwa, Catherine A. Foss, Rina Murai, Samantha de los Reyes, Atsushi Kamiya, Yolanda Mateo, Patricio O'Donnell, Nicola G. Cascella, Toshitaka Nabeshima, Tomás R. Guilarte, Martin G. Pomper, Akira Sawa

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Imaging of the human brain has been an invaluable aid in understanding neuropsychopharmacology and, in particular, the role of dopamine in the striatum in mental illness. Here, we report a study in a genetic mouse model for major mental illness guided by results from human brain imaging: a systematic study using small animal positron emission tomography (PET), autoradiography, microdialysis and molecular biology in a putative dominant-negative mutant DISC1 transgenic model. This mouse model showed augmented binding of radioligands to the dopamine D2 receptor (D2R) in the striatum as well as neurochemical and behavioral changes to methamphetamine administration. Previously we reported that this model displayed deficits in the forced swim test, a representative indicator of antidepressant efficacy. By combining the results of our two studies, we propose a working hypothesis for future studies that this model might represent a mixed condition of depression and psychosis. We hope that this study will also help bridge a major gap in translational psychiatry between basic characterization of animal models and clinico-pharmacological assessment of patients mainly through PET imaging.

Original languageEnglish
Pages (from-to)1574-1580
Number of pages7
JournalHuman molecular genetics
Volume22
Issue number8
DOIs
Publication statusPublished - 01-04-2013
Externally publishedYes

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Molecular Imaging
Neuroimaging
Positron-Emission Tomography
Dopamine D2 Receptors
Methamphetamine
Genetic Models
Microdialysis
Autoradiography
Psychotic Disorders
Antidepressive Agents
Psychiatry
Molecular Biology
Dopamine
Animal Models
Pharmacology
Depression

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Jaaro-Peled, H., Niwa, M., Foss, C. A., Murai, R., Reyes, S. D. L., Kamiya, A., ... Sawa, A. (2013). Subcortical dopaminergic deficits in a DISC1 mutant model: A study in direct reference to human molecular brain imaging. Human molecular genetics, 22(8), 1574-1580. https://doi.org/10.1093/hmg/ddt007
Jaaro-Peled, Hanna ; Niwa, Minae ; Foss, Catherine A. ; Murai, Rina ; Reyes, Samantha de los ; Kamiya, Atsushi ; Mateo, Yolanda ; O'Donnell, Patricio ; Cascella, Nicola G. ; Nabeshima, Toshitaka ; Guilarte, Tomás R. ; Pomper, Martin G. ; Sawa, Akira. / Subcortical dopaminergic deficits in a DISC1 mutant model : A study in direct reference to human molecular brain imaging. In: Human molecular genetics. 2013 ; Vol. 22, No. 8. pp. 1574-1580.
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Jaaro-Peled, H, Niwa, M, Foss, CA, Murai, R, Reyes, SDL, Kamiya, A, Mateo, Y, O'Donnell, P, Cascella, NG, Nabeshima, T, Guilarte, TR, Pomper, MG & Sawa, A 2013, 'Subcortical dopaminergic deficits in a DISC1 mutant model: A study in direct reference to human molecular brain imaging', Human molecular genetics, vol. 22, no. 8, pp. 1574-1580. https://doi.org/10.1093/hmg/ddt007

Subcortical dopaminergic deficits in a DISC1 mutant model : A study in direct reference to human molecular brain imaging. / Jaaro-Peled, Hanna; Niwa, Minae; Foss, Catherine A.; Murai, Rina; Reyes, Samantha de los; Kamiya, Atsushi; Mateo, Yolanda; O'Donnell, Patricio; Cascella, Nicola G.; Nabeshima, Toshitaka; Guilarte, Tomás R.; Pomper, Martin G.; Sawa, Akira.

In: Human molecular genetics, Vol. 22, No. 8, 01.04.2013, p. 1574-1580.

Research output: Contribution to journalArticle

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T2 - A study in direct reference to human molecular brain imaging

AU - Jaaro-Peled, Hanna

AU - Niwa, Minae

AU - Foss, Catherine A.

AU - Murai, Rina

AU - Reyes, Samantha de los

AU - Kamiya, Atsushi

AU - Mateo, Yolanda

AU - O'Donnell, Patricio

AU - Cascella, Nicola G.

AU - Nabeshima, Toshitaka

AU - Guilarte, Tomás R.

AU - Pomper, Martin G.

AU - Sawa, Akira

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