Reduced cholesterol is associated with the depressive-like behavior in rats through modulation of the brain 5-HT1A receptor

Abstract

BackgroundLow 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.MethodsIn 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.ResultsCMS 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.ConclusionThis 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.

The Role of Lipid Biomarkers in Major Depression

“…Indeed, it has been shown that increased HDL and omega-3 PUFAs could protect against depression-mediated inflammation [74,152]. The precise mechanics of inflammatory processes continues to place protein dysfunction as a key aspect of MDD pathophysiology, but the role of lipids is proving to be just as important, especially since protein function at the molecular level is largely determined by lipid function.…”

“…Low cholesterol content in cell membranes is associated with decreased density of 5-HT receptors measured in in vitro mouse analysis [72,73,74]. Sun et al exposed rats to chronic mild stress (CMS) for 28 days and showed significantly reduced total cholesterol level in the medial prefrontal cortex (mPFC) [74]. Chronic dietary supplementation reversed the behaviours induced by CMS.…”

“…Chronic dietary supplementation reversed the behaviours induced by CMS. Furthermore, injection of a 5-HT1A antagonist into the mPFC blocked the treatment effects of cholesterol supplementation [74]. This suggests that cholesterol, particularly in the prefrontal cortex, influences the sensitivity of the 5-HT1A receptor in the pathology and treatment of depression.…”

Dietary essential oil from navel orange alleviates depression in reserpine‐treated mice by monoamine neurotransmitters

“…In addition, accumulating evidence suggests that various psychiatric disorders including depression can be affected by the altered lipids levels (TC, TG, LDL, and HDL) . Lipids are found to be involved in the neuronal function of the brain, influencing emotional behaviours and mental disorders . Depression and elevated total cholesterol are identified as an independent and potent risk factor for cardiovascular disease .…”

“…18,19 Lipids are found to be involved in the neuronal function of the brain, influencing emotional behaviours and mental disorders. 20 Depression and elevated total cholesterol are identified as an independent and potent risk factor for cardiovascular disease. 21 There is growing evidence that high TC levels may have influence on the serotoninergic activity in the brain and may be the cause of poor uptake of 5-HT from the bloodn.…”