Association between polymorphism c.1-765G&gt;C of the COX2 gene and cognitive impairment in individuals 65 years or more with diabetes from a Geriatric Service in Monterrey, Mexico

González, Efraín Salas; Hermosillo, Hugo Gutiérrez; Rodrigez, J.; Romero, Miguel Arturo Reyes; Camacho‐Luis, Abelardo; Corona, Rebeca Palacios; Nava, Jorge Alberto Burciaga; Valles, José Alejandro Ríos; Pérez, Hernán

doi:10.1016/j.medcli.2013.07.031

Cited by 2 publications

(1 citation statement)

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“…In Mexican patients with diabetes [28], less exposure to the CG genotype of the c.1-765G>C polymorphism of COX2 was shown to be associated with minor cognitive decline. COX2-specific inhibitors, in treating brain injuries, improve functional outcomes in rat model of traumatic brain injury.…”

Section: Discussionmentioning

confidence: 99%

cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress

Luo

Kuang

et al. 2017

Oncotarget

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To investigate the mechanism of cyclooxygenase 2 (COX2) in learning and memory impairments in rats subjected to chronic unpredictable mild stress (CUMS), meloxicam was used intragastrically to inhibit the activity of cyclooxygenase 2. Moreover, cyclooxygenase 2 over-expressing or RNA interfere lentivirus was injected intraventricularly to increase or decrease the enzyme's expression, respectively. The body weights and sucrose consumption were used to analyze depressive behaviors, while the Morris water maze and step-down-type passive avoidance tests were carried out to evaluate the learning-memory functions. The levels of inflammatory cytokines were measured to estimate inflammation and the contents of cyclic adenosine monophosphate (cAMP) were used to measure the levels of the second messenger. Changes in cyclooxygenase 2 mRNA levels were analyzed using reverse transcription polymerase chain reaction. Moreover, the expression of cyclooxygenase 2, brain-derived neurotrophic factor (BDNF), prostaglandins receptor 3 (EP3), protein kinase A (PKA), cAMP response element binding protein (CREB), and phosphorylated CREB were estimated using immunohistochemical staining or western blotting. The results showed that CUMS led to significant depressive-like behaviors and learning and memory dysfunctions. Also, the cAMP levels decreased significantly, while levels of inflammatory cytokines and prostaglandins E2 increased significantly. The expressions of PKA, BDNF, phosphorylated CREB/CREB declined and cyclooxygenase 2 was increased. Meloxicam and cyclooxygenase 2 RNA interfere lentivirus reversed the changes caused by CUMS while cyclooxygenase 2-overexpressing lentivirus worsened these abnormalities. The findings also showed that CUMS increased cyclooxygenase 2 expression, which can cause learning and memory impairments, mainly through activating the hippocampal neuronal cAMP/PKA-CREB-BDNF signaling pathways.

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Section: Discussionmentioning

confidence: 99%

cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress

Luo

Kuang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

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Common and Rare Genetic Variants Associated With Alzheimer's Disease

et al. 2015

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Alzheimer's disease (AD) is one of the most devastating disorders. Despite the continuing increase of its incidence among aging populations, no effective cure has been developed mainly due to difficulties in early diagnosis of the disease before damaging of the brain, and the failure to explore its complex underlying molecular mechanisms. Recent technological advances in genome-wide association studies (GWAS) and high throughput next generation whole genome, and exome sequencing had deciphered many of AD-related loci, and discovered single nucleotide polymorphisms (SNPs) that are associated with altered AD molecular pathways. Highlighting altered molecular pathways linked to AD pathogenesis is crucial to identify novel diagnostic and therapeutic AD targets.

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Association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in individuals 65 years or more with diabetes from a Geriatric Service in Monterrey, Mexico

Cited by 2 publications

References 36 publications

cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress

cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress

Common and Rare Genetic Variants Associated With Alzheimer's Disease

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