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排序方式: 共有1485条查询结果,搜索用时 15 毫秒
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Raul A. Bastarrachea MD Juan C. López-Alvarenga MD PhD Raúl Calzada-León MD Sara Arellano-Montaño MD Jorge Gonzalez-Barranco MD Rafael Violante-Ortíz MD Blanca Estela Del-Rio-Navarro MD Agustín Lara-Esqueda MD Pedro Pérez MD Guillermo Fanghänel MD Agustín Madero MD Arturo Berber MD PhD 《Advances in therapy》2006,23(3):506-509
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Albasanz JL Rodríguez A Ferrer I Martín M 《The European journal of neuroscience》2007,26(12):3501-3508
The adenosine A1 receptor (A1 R)–adenylyl cyclase (AC) pathway was studied in post-mortem human frontal and occipital cortex from Pick's disease (PiD) cases and age-matched nondemented controls. In frontal cortex, the main brain area affected in PiD, A1 Rs, determined by radioligand binding, Western blotting and real-time PCR assays, were significantly increased in PiD samples, suggesting up-regulation of this receptor. AC activity was determined in basal and stimulated conditions via stimulatory guanine nucleotide binding proteins (Gs) using GTP, or directly with forskolin. Basal AC activity was reduced in brains from PiD cases. This agrees with the decrease in AC type I (AC I) level detected by Western blotting. However, inhibition of forskolin-stimulated AC activity by a selective A1 R agonist was significantly increased in brains from PiD. In occipital cortex, adenosine A1 R numbers were similar in control and PiD cases, and no significant differences were found in A1 R-mediated AC inhibition. These results show that the adenosine A1 R–AC transduction pathway is specifically up-regulated and sensitized in frontal cortex brain in PiD. 相似文献
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Marta Llansola Carmina Montoliu Omar Cauli Vicente Hernández-Rabaza Ana Agustí Andrea Cabrera-Pastor Carla Giménez-Garzó Alba González-Usano Vicente Felipo 《Metabolic brain disease》2013,28(2):151-154
This mini-review focus on our studies on alterations in glutamatergic neurotransmission and their role in neurological alterations in rat models of chronic hyperammonemia and hepatic encephalopathy (HE). Hyperammonemia impairs the glutamate-nitric oxide (NO)-cGMP pathway in cerebellum, which is responsible for reduced learning ability. We studied the underlying mechanisms and designed treatments to restore the pathway and learning. This was achieved by treatment with: phosphodiesterase 5 inhibitors, cGMP, anti-inflammatories (ibuprofen), p38 inhibitors or GABAA receptor antagonists (bicuculline). Hyperammonemia alters signal transduction associated to metabotropic glutamate receptors (mGluRs). Hypokinesia in hyperammonemia and HE is due to increased extracellular glutamate and mGluR1 activation in substantia nigra; blocking this receptor restores motor activity. The motor responses to mGluRs activation in nucleus accumbens (NAcc) are altered in hyperammonemia and HE, with reduced dopamine and increased glutamate release. This leads to activation of different neuronal circuits and enhanced motor responses. These studies show that altered responses to activation of NMDA receptors and mGluRs play essential roles in cognitive and motor alterations in hyperammonemia and HE and provide new treatments restoring cognitive and motor function. 相似文献
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González A Sáez ME Aragón MJ Galán JJ Vettori P Molina L Rubio C Real LM Ruiz A Ramírez-Lorca R 《Human reproduction (Oxford, England)》2006,21(4):943-951
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The aim of the present study was to investigate the role of CALPAIN-5 (CAPN5) gene in PCOS susceptibility. METHODS: We analysed four intronic polymorphisms of the CAPN5 gene in 148 well-characterized women with PCOS and 606 unrelated controls. We performed a case-control study and an intracohort analysis of clinical characteristics associated with PCOS. RESULTS: Analysis of haplotypes distribution between PCOS population compared to controls showed a strong deviation (P = 0.00029). The haplotypes GGCA and GGTG were overrepresented in PCOS patients (P = 0.009 and P = 0.001, respectively). In addition, we identified several CAPN5 haplotypes associated with phenotypic differences observed between PCOS patients, such as the presence of obesity (P = 0.02), cardiovascular complications (P = 0.02), familial antecedents of obesity (P = 0.003) and of hypertension (P = 0.007) and type 2 diabetes mellitus aggregation (P = 0.04). CONCLUSIONS: These results suggest a role of CAPN5 gene in PCOS susceptibility in humans. Moreover, novel candidate risk alleles have been identified, within CAPN5 gene, which could be associated with important phenotypic and prognosis differences observed in PCOS patients. 相似文献
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Adenosine A2A receptors (A2AR) are highly expressed in striatum. However, they are also present in extrastriatal structures. A2AR were studied in post-mortem human frontal cortex from Pick's disease (PiD) and age-matched non-demented controls by radioligand binding assays, Western-blotting, real-time PCR and adenylyl cyclase activity determination. Saturation binding assay using [3H]ZM 241385, a selective A2A antagonist, as radioligand revealed a significant increase in total adenosine A2AR numbers (Bmax) in frontal cortex from PiD samples (191% of control Bmax), suggesting up-regulation of this receptor. A significant increase in the level of A2AR was also detected by Western-blotting. Furthermore, expression of mRNA coding A2AR determined by quantitative real-time PCR was enhanced. In agreement, stimulation of adenylyl cyclase by CGS 21680, a selective A2A receptor agonist, was significantly strengthened. Up-regulation of A2B receptors and their corresponding mRNA was also observed. These results show that A2A adenosine receptor/adenylyl cyclase transduction pathway is up-regulated and sensitized in frontal cortex brain from PiD. 相似文献