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高脂肪饮食对雌性大鼠前额叶皮层大麻素 CB(1) 受体功能的影响。

Changes in cannabinoid CB(1) receptor functionality in the female rat prefrontal cortex following a high fat diet.

机构信息

Department of Public Health and Clinical Medicine, Medicine, Umeå University, SE-901 87 Umeå, Sweden.

出版信息

Life Sci. 2013 Apr 19;92(13):757-62. doi: 10.1016/j.lfs.2013.02.002. Epub 2013 Feb 20.

DOI:10.1016/j.lfs.2013.02.002
PMID:23454443
Abstract

AIMS

A high fat diet (HFD) has been found to affect neurotransmission in the prefrontal cortex, but the effects of this dietary regime upon the endocannabinoid system has not been studied in this brain region. In consequence, in the present study, we have investigated the effect of HFD for up to 20 weeks upon the endocannabinoid system in the prefrontal cortex of female rats.

MAIN METHODS

CB1 receptor functionality was measured using CP55,940-stimulated [(35)S]GTPγS autoradiography. Fatty acid amide hydrolase and monoacylglycerol lipase activities were analysed in brain regions by assessing rates of [(3)H]anandamide and JZL184-sensitive [(3)H]2-oleoylglycerol hydrolysis, respectively.

KEY FINDINGS

In the prefrontal cortex, a significantly greater stimulation of [(35)S]GTPγS binding by CP55,940 was seen following 4-12, but not 16-20 weeks of HFD. No significant changes were seen for the caudate-putamen, CA1-CA3 region of the hippocampus or the dentate gyrus. The increased response for the 12 week animals was not accompanied by a significant change in the receptor density, measured with [(3)H]CP55,940 autoradiography. No significant changes in the activity of the endocannabinoid hydrolytic enzymes fatty acid amide or monoacylglycerol lipase were seen in the prefrontal cortex, hippocampus, amygdala or hypothalamus following either 12 or 20 weeks of HFD.

SIGNIFICANCE

It is concluded that HFD produces an increased CB1 receptor functionality in the prefrontal cortex of female rats. Given that the endocannabinoid system regulates neurotransmission in the prefrontal cortex, the present data would implicate this system in the disturbed prefrontal cortical activity in this region following a high fat diet.

摘要

目的

高脂肪饮食(HFD)已被发现会影响前额叶皮层的神经递质传递,但这种饮食方式对该脑区的内源性大麻素系统的影响尚未在该脑区进行研究。因此,在本研究中,我们调查了长达 20 周的 HFD 对雌性大鼠前额叶皮层内源性大麻素系统的影响。

主要方法

使用 CP55,940 刺激[35S]GTPγS 放射自显影测量 CB1 受体功能。通过评估[3H]花生四烯酸酰胺和 JZL184 敏感[3H]2-油酰甘油水解的速率,分别在脑区分析脂肪酸酰胺水解酶和单酰基甘油脂肪酶的活性。

主要发现

在前额叶皮层中,CP55,940 刺激[35S]GTPγS 结合的显著增加见于 4-12 周,但不是 16-20 周的 HFD。纹状体、海马 CA1-CA3 区或齿状回未见明显变化。12 周动物的反应增加并不伴有[3H]CP55,940 放射自显影测量的受体密度的显著变化。在 HFD 12 或 20 周后,在前额叶皮层、海马、杏仁核或下丘脑均未观察到内源性大麻素水解酶脂肪酸酰胺或单酰基甘油脂肪酶的活性发生显著变化。

结论

HFD 导致雌性大鼠前额叶皮层 CB1 受体功能增强。鉴于内源性大麻素系统调节前额叶皮层的神经递质传递,本数据提示该系统参与了高脂肪饮食后该区域前额叶皮质活动的紊乱。

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