title: Theobromine-Induced Changes in A1 Purinergic Receptor Gene Expression and Distribution in a Rat Brain Alzheimer's Disease Model.
abstract: 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.
authors: Laboratorio de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, Querétaro, México.
authors: Jesus
authors: J
authors: Mendiola-Precoma
authors: Laboratorio de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, Querétaro, México.
authors: Karla
authors: K
authors: Padilla
authors: Laboratorio de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, Querétaro, México.
authors: Alfredo
authors: A
authors: Rodríguez-Cruz
authors: Laboratorio de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, Querétaro, México.
authors: Laura C
authors: LC
authors: Berumen
authors: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Juriquilla, Querétaro, CP, Mexico.
authors: Ricardo
authors: R
authors: Miledi
authors: Laboratorio de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario S/N, Querétaro, México.
authors: Guadalupe
authors: G
authors: García-Alcocer
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D013805:Theobromine / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D016229:Amyloid beta-Peptides; D053583:Interleukin-1beta; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D014665:Vasodilator Agents; D002784:Cholesterol; D013805:Theobromine
keywords: Adenosine; Alzheimer’s disease; cholesterol; lard; oxidative stress; purinergic receptors; theobromine