期刊
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
卷 110, 期 -, 页码 174-179出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2018.12.003
关键词
PET imaging; Dopamine; D2; Schizophrenia; Striatum; Cortex; Mouse model; Translation and back-translation
资金
- National Institute of Mental Health (NIMH): Sylvio O. Conte Center for the Study of Dopamine Dysfunction in Schizophrenia [P50 MH086404]
Despite multiple lines of research, a mechanistic understanding of schizophrenia remains elusive. Neuroimaging studies have yielded observations that can be used in translational studies in animals to attempt to uncover their cellular and circuit basis and their significance for the diseased human brain. Enhanced D2 stimulation in the striatum is a well replicated and established observation in patients with schizophrenia. This bedside observation was reproduced at the bench level by creating a transgenic mouse overexpressing D2 receptors in dorsal striatum (D2R-OE mouse). The D2R-OE mouse showed multiple behavioral, molecular, electro-physiological and anatomical alterations. Some of these are consistent with findings in patients with schizophrenia, providing construct validity to the model and mechanistic insights for the observations made in humans. Other findings were novel, and provide an opportunity for a reverse translational effort back into the clinic. In this review we will summarize the process of translation and back translation from the D2R-OE mouse and describe the insights into the pathophysiology of the disease gained through this type of translational work.
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