title: Reduced cholesterol is associated with the depressive-like behavior in rats through modulation of the brain 5-HT1A receptor.
abstract: BACKGROUND
  Low serum cholesterol levels are related to an increased risk of depression and its serious consequences. However, the effect of central cholesterol on depressive disorder and its potential regulatory mechanism is poorly understood. Therefore, brain cholesterol in patients with depression may not only decrease the risk for developing this disease but also increase the beneficial effects of treatment for depression.
  
  
  METHODS
  In current study, rats were exposed to chronic mild stress (CMS) for consecutive 28 days, and the depressive-like behavior was tested by sucrose preference test, immobility in the forced swim test, locomotor activity in the open field test, decreased bodyweight and food intake. Additionally, the total cholesterol levels in the medial prefrontal cortex (mPFC) and the hippocampus of rats were measured by gas chromatograph mass spectrometer. Finally, 5-HT1A receptor antagonist WAY100635 was used to determine the potential role of serotonin system in the interaction between central cholesterol and depression.
  
  
  RESULTS
  CMS significantly reduced total cholesterol levels in the mPFC but not in the hippocampus and resulted in depressive-like behavior. Chronic supplementation of cholesterol by food reversed the depressive-like behavior induced by CMS. Furthermore, pre-injection of 5-HT1A receptor antagonist WAY100635 into the mPFC blocked the treatment effects of cholesterol on the reversal of behavioral response.
  
  
  CONCLUSIONS
  This finding suggested that cholesterol in the mPFC may have an impact on the sensitivity of the 5-HT1A receptor in the development and treatment of depression. The treatment benefits of cholesterol could be through modulation of the brain 5-HT1A receptor.
authors.affiliation: Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, 16, Jiangsu Road, Qingdao, Shandong Province, 266000, China. sunsq_ahqu@163.com.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of the Intensive Care Unit, The Affiliated Hospital of Qingdao University, 16, Jiangsu Road, Qingdao, Shandong Province, 266000, China. yangs_ahqu@163.com.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, 16, Jiangsu Road, Qingdao, Shandong Province, 266000, China. maoyj_ahqu@163.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, 16, Jiangsu Road, Qingdao, Shandong Province, 266000, China. jiaxj_ahqu@163.com.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, 16, Jiangsu Road, Qingdao, Shandong Province, 266000, China. drzhangz_ahqu@163.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000032:analysis*; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry; D006624:Hippocampus / Q000737:chemistry*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000737:chemistry*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000150:complications
chemical_list: D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D002784:Cholesterol