Sun Shuqin, Yang Shuo, Mao Yongjun, Jia Xiujuan, Zhang Zheng
Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, 16, Jiangsu Road, Qingdao, Shandong Province, 266000, China.
Department of the Intensive Care Unit, The Affiliated Hospital of Qingdao University, 16, Jiangsu Road, Qingdao, Shandong Province, 266000, China.
Lipids Health Dis. 2015 Mar 24;14:22. doi: 10.1186/s12944-015-0020-7.
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.
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.
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.
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.
低血清胆固醇水平与抑郁症风险增加及其严重后果相关。然而，中枢胆固醇对抑郁症的影响及其潜在调节机制尚不清楚。因此，抑郁症患者大脑中的胆固醇可能不仅会降低患此病的风险，还会增强抑郁症治疗的有益效果。
在本研究中，将大鼠连续28天暴露于慢性轻度应激（CMS），通过蔗糖偏好试验、强迫游泳试验中的不动时间、旷场试验中的运动活动、体重减轻和食物摄入量来测试其抑郁样行为。此外，用气相色谱 - 质谱仪测量大鼠内侧前额叶皮质（mPFC）和海马中的总胆固醇水平。最后，使用5 - HT1A受体拮抗剂WAY100635来确定血清素系统在中枢胆固醇与抑郁症相互作用中的潜在作用。
CMS显著降低了mPFC中的总胆固醇水平，但未降低海马中的总胆固醇水平，并导致了抑郁样行为。通过食物长期补充胆固醇可逆转CMS诱导的抑郁样行为。此外，预先向mPFC注射5 - HT1A受体拮抗剂WAY100635可阻断胆固醇对行为反应逆转的治疗效果。
这一发现表明，mPFC中的胆固醇可能在抑郁症的发生和治疗中对5 - HT1A受体的敏感性产生影响。胆固醇的治疗益处可能是通过调节大脑5 - HT1A受体实现的。
