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Depressive-Like Behaviors in a Rat Model of Chronic Cerebral Hypoperfusion

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Abstract

The vascular depression hypothesis suggests that there is an association between cerebrovascular pathophysiology and depression in the elderly. We investigated depressive-like behaviors and perturbations in the hypothalamus-pituitary-adrenal (HPA) axis in a rat model of chronic cerebral hypoperfusion. We modeled chronic cerebral hypoperfusion by permanent occlusion of the bilateral common carotid arteries (BCCAo) in Wistar rats. Sucrose preference, forced swim, and social interaction tests were performed to measure depressive-like behaviors. The plasma levels of adrenocorticotropic hormone and corticosterone, and the hippocampal expression of the glucocorticoid receptor (GR) were assessed. Sucrose preference (P = 0.045) and social withdrawal (P = 0.038) were significantly enhanced in BCCAo rats. Increased plasma levels of corticosterone (P = 0.034) and impaired cytosolic-to-nuclear translocation of the GR protein were observed in the hippocampus (P = 0.038) of BCCAo rats. Our experimental results support the clinical hypothesis that vascular depression can be induced by chronic cerebral hypoperfusion. Increased HPA axis activity and perturbation of the GR signaling pathway in the hippocampus may be associated with depressive-like behaviors in rats with chronic cerebral hypoperfusion.

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Conflict of Interest

Sang Rim Lee, Bo-Ryoung Choi, Saswati Paul, Ju-Ha Seo, Dong Bin Back, Jung-Soo Han, Dong-Hee Choi, Kyoung Ja Kwon, Chan Young Shin, Jongmin Lee, Seol-Heui Han, and Hahn Young Kim declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010–0008867).

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Authors and Affiliations

  1. Department of Neurology, Center for Geriatric Neuroscience Research, Institute of Biomedical Science and Technology, Research Institute of Medical Science, School of Medicine, Konkuk University, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, 143-729, Republic of Korea

    Sang Rim Lee, Boryoung Choi, Ju-Ha Seo, Dong Bin Back, Kyoung Ja Kwon, Seol-Heui Han & Hahn Young Kim

  2. Department of Biological Sciences, Konkuk University, Seoul, Republic of Korea

    Sang Rim Lee, Boryoung Choi, Saswati Paul & Jung-Soo Han

  3. Department of Medicine, Center for Geriatric Neuroscience Research, Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul, Republic of Korea

    Dong-Hee Choi

  4. Department of Pharmacology, Center for Geriatric Neuroscience Research, Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul, Republic of Korea

    Chan Young Shin

  5. Department of Rehabilitation Medicine, Center for Geriatric Neuroscience Research, Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul, Republic of Korea

    Jongmin Lee

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  1. Sang Rim Lee
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Correspondence to Hahn Young Kim.

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Lee, S.R., Choi, B., Paul, S. et al. Depressive-Like Behaviors in a Rat Model of Chronic Cerebral Hypoperfusion. Transl. Stroke Res. 6, 207–214 (2015). https://doi.org/10.1007/s12975-014-0385-3

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  • DOI: https://doi.org/10.1007/s12975-014-0385-3

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