关键词: Autoradiography CB1 Minipig Sucrose Synaptic vesicle glycoprotein 2A mGluR5

Mesh : Animals Swine, Miniature Swine Sucrose / administration & dosage Male Receptor, Metabotropic Glutamate 5 / metabolism Receptors, Cannabinoid / metabolism Synapses / metabolism drug effects Receptor, Cannabinoid, CB1 / metabolism Receptors, Dopamine D2 / metabolism Brain / metabolism drug effects Female Receptors, Dopamine D3 / metabolism

来  源:   DOI:10.1016/j.neuropharm.2024.110018

Abstract:
Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and metabolic syndrome. Clinical studies link unhealthy diets with the development of mental health disorders, particularly depression. Here, we investigate the effects of 12 days of sucrose consumption administered as 2 L of 25% sucrose solution daily for 12 days in Göttingen minipigs on the function of brain receptors involved in reward and motivation, regulating feeding, and pre- and post-synaptic mechanisms. Through quantitative autoradiography of cryostat sections containing limbic brain regions, we investigated the effects of sucrose restricted to a 1-h period each morning, on the specific binding of [3H]raclopride on dopamine D2/3 receptors, [3H]UCB-J at synaptic vesicle glycoprotein 2A (SV2A), [3H]MPEPγ at metabotropic glutamate receptor subtype 5 (mGluR5) and [3H]SR141716A at the cannabinoid receptor 1 (CB1). Compared to control diet animals, the sucrose group showed significantly lower [3H]UCB-J and [3H]MPEPγ binding in the prefrontal cortex. The sucrose-consuming minipigs showed higher hippocampal CB1 binding, but unaltered dopamine D2/3 binding compared to the control group. We found that the sucrose diet reduced the synaptic density marker while increasing CB1 binding in limbic brain structures, which may subserve maladaptive changes in appetite regulation and feeding. Further studies of the effects of diets and lifestyle habits on brain neuroreceptor and synaptic density markers are warranted.
摘要:
富含蔗糖和脂肪的饮食在世界各地变得越来越普遍,伴随着心血管疾病患病率的上升,癌症,糖尿病,肥胖,和代谢综合征。临床研究将不健康的饮食与心理健康障碍的发展联系起来,尤其是抑郁症。这里,我们调查了12天的蔗糖消耗作为2升25%的蔗糖溶液每天在哥廷根小型猪12天对大脑受体参与奖励和动机的功能的影响,调节喂养,以及突触前和突触后机制。通过对包含边缘脑区的低温恒温器切片进行定量放射自显影,我们研究了限制在每天早晨1小时内的蔗糖的影响,[3H]雷氯必利对多巴胺D2/3受体的特异性结合,[3H]UCB-J在突触小泡糖蛋白2A(SV2A),[3H]MPEPγ在代谢型谷氨酸受体亚型5(mGluR5)和[3H]SR141716A在大麻素受体1(CB1)。与对照饮食动物相比,蔗糖组[3H]UCB-J和[3H]MPEPγ在前额叶皮层的结合显著降低。耗糖的小型猪表现出更高的海马CB1结合,但与对照组相比,多巴胺D2/3结合没有改变。我们发现,蔗糖饮食降低了突触密度标记,同时增加了边缘脑结构中的CB1结合,这可能会导致食欲调节和进食方面的适应不良变化。需要进一步研究饮食和生活习惯对脑神经受体和突触密度标志物的影响。
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