Pitx3 deficient mice as a genetic animal model of co-morbid depressive disorder and parkinsonism

Kyoung Shim Kim, Young Mi Kang, Tae Shin Park, Hye Yeon Park, Yoon Jung Kim, Baek Soo Han, Chun Hyung Kim, Chul Ho Lee, Paul A. Ardayfio, Pyung Lim Han, Bong Hyun Jung, Kwang Soo Kim

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish
Pages (from-to)72-81
Number of pages10
JournalBrain Research
StatePublished - 13 Mar 2014

Bibliographical note

Funding Information:
This work was supported by a Grant from KRIBB Research Initiative Program, the Basic Science Research Program through the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MEST) ( 2012R1A2A2A02014520 ), the Next-Generation BioGreen 21 Program (No. PJ008022022012) , Rural Development Administration, Republic of Korea , and National Institute of Health Grants ( MH48866 , NS070577 and MH87903 ). The authors thank Dong-Hee Choi for technical assistance.


  • Depression
  • Parkinson's disease
  • Stress
  • c-Fos


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