Pitx3 deficient mice as a genetic animal model of co-morbid depressive disorder and parkinsonism.
Approximately 40-50% of all patients with Parkinson׳s disease (PD) show symptoms and signs of depressive disorders, for which neither pathogenic understanding nor rational treatment are available. Using Pit3x-deficient mice, a model for selective nigrostriatal dopaminergic neurodegeneration, we tested depression-related behaviors and acute stress responses to better understand how a nigrostriatal dopaminergic deficit increases the prevalence of depressive disorders in PD patients. Pitx3-deficient mice showed decreased sucrose consumption and preference in the two-bottle free-choice test of anhedonia. Acute restraint stress increased c-Fos (known as a neuronal activity marker) expression levels in various brain regions, including the prefrontal cortex, striatum, nucleus accumbens, and paraventricular nucleus of the hypothalamus (PVN), in both Pitx3+/+ and -/- mice. However, the stress-induced increases in c-Fos levels in the cortex, dorsal striatum, and PVN were significantly greater in Pitx3-/- than +/+ mice, suggesting that signs of depressive disorders in parkinsonism are related to altered stress vulnerability. Based on these results, we propose that Pitx3-/- mice may serve as a useful genetic animal model for co-morbid depressive disorder and parkinsonism.
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea. Electronic address: kskim@kribb.re.kr.
Kyoung-Shim
KS
Kim
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
Young-Mi
YM
Kang
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
Young
Y
Kang
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
Tae-Shin
TS
Park
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
Hye-Yeon
HY
Park
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
Yoon-Jung
YJ
Kim
Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
Baek-Soo
BS
Han
Molecular Neurobiology Laboratory, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Chun-Hyung
CH
Kim
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
Chul-Ho
CH
Lee
Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN 46285, USA.
Paul A
PA
Ardayfio
Department of Chemistry and Nano Science, Department of Brain & Cognitive Sciences, Ewha Woman׳s University, Seoul 120-750, Republic of Korea.
Pyung-Lim
PL
Han
BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology and Nanobiotechnology Major School of Engineering, University of Science and Technology, Daejeon 305-806, Republic of Korea.
Bong-Hyun
BH
Jung
Molecular Neurobiology Laboratory, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA. Electronic address: kskim@mclean.harvard.edu.
Kwang-Soo
KS
Kim
D059445:Anhedonia / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015897:Comorbidity; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior; D005260:Female; D005786:Gene Expression Regulation; D016762:Genes, fos; D018398:Homeodomain Proteins / Q000235:genetics; D007099:Imipramine / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000523:psychology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000150:complications*; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
D000928:Antidepressive Agents; D019422:Dietary Sucrose; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; C433629:homeobox protein PITX3; D007099:Imipramine; D003345:Corticosterone
Depression; Parkinson׳s disease; Stress; c-Fos