Abstract
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 language | English |
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Pages (from-to) | 72-81 |
Number of pages | 10 |
Journal | Brain Research |
Volume | 1552 |
DOIs | |
State | Published - 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.
Keywords
- Depression
- Parkinson's disease
- Stress
- c-Fos