Mendiola-Precoma Jesus, Padilla Karla, Rodríguez-Cruz Alfredo, Berumen Laura C, Miledi Ricardo, García-Alcocer Guadalupe
Laboratorio de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, Querétaro, México.
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Juriquilla, Querétaro, CP, Mexico.
J Alzheimers Dis. 2017;55(3):1273-1283. doi: 10.3233/JAD-160569.
Dementia caused by Alzheimer's disease (AD) is mainly characterized by accumulation in the brain of extra- and intraneuronal amyloid-β (Aβ) and tau proteins, respectively, which selectively affect specific regions, particularly the neocortex and the hippocampus. Sporadic AD is mainly caused by an increase in apolipoprotein E, a component of chylomicrons, which are cholesterol transporters in the brain. Recent studies have shown that high lipid levels, especially cholesterol, are linked to AD. Adenosine is an atypical neurotransmitter that regulates a wide range of physiological functions by activating four P1 receptors (A1, A2A, A2B, and A3) and P2 purinergic receptors that are G protein-coupled. A1 receptors are involved in the inhibition of neurotransmitter release, which could be related to AD. The aim of the present work was to study the effects of a lard-enriched diet (LED) on cognitive and memory processes in adult rats (6 months of age) as well as the effect of theobromine on these processes. The results indicated that the fat-enriched diet resulted in a long-term deterioration in cognitive and memory functions. Increased levels of Aβ protein and IL-1β were also observed in the rats fed with a high-cholesterol diet, which were used to validate the AD animal model. In addition, the results of qPCR and immunohistochemistry indicated a decrease in gene expression and distribution of A1 purinegic receptor, respectively, in the hippocampus of LED-fed rats. Interestingly, theobromine, at both concentrations tested, restored A1 receptor levels and improved cognitive functions and Aβ levels for a dose of 30 mg/L drinking water.
阿尔茨海默病（AD）所致痴呆的主要特征是细胞外和细胞内分别积累淀粉样β蛋白（Aβ）和tau蛋白，这些蛋白会选择性地影响特定区域，尤其是新皮质和海马体。散发性AD主要由载脂蛋白E增加所致，载脂蛋白E是乳糜微粒的一种成分，而乳糜微粒是大脑中的胆固醇转运体。最近的研究表明，高血脂水平，尤其是胆固醇，与AD有关。腺苷是一种非典型神经递质，它通过激活四种P1受体（A1、A2A、A2B和A3）以及G蛋白偶联的P2嘌呤能受体来调节广泛的生理功能。A1受体参与抑制神经递质释放，这可能与AD有关。本研究的目的是研究富含猪油的饮食（LED）对成年大鼠（6月龄）认知和记忆过程的影响以及可可碱对这些过程的影响。结果表明，富含脂肪的饮食导致认知和记忆功能长期恶化。在喂食高胆固醇饮食的大鼠中还观察到Aβ蛋白和白细胞介素-1β水平升高，这些大鼠被用于验证AD动物模型。此外，qPCR和免疫组织化学结果表明，喂食LED的大鼠海马体中A1嘌呤能受体的基因表达和分布分别减少。有趣的是，在所测试的两种浓度下，可可碱都能恢复A1受体水平，并在饮用30mg/L水的剂量下改善认知功能和Aβ水平。
