Although the precise mechanism is unknown, neuron apoptosis is believed to participate in neuropathy caused by acrylamide (ACR). Telomerase reverse transcriptase (TERT) exhibits an anti-apoptotic function, but its contribution to the pathogenesis of ACR neurotoxicity is unclear. We investigated adult male rats that were given 30, 40 and 50 mg/kg ACR three times/week for 4 weeks. We found that ACR treatment caused significant deficits in sensory/motor function as measured by gait score, landing foot spread distance, movement initiation test and tail immersion test. Histological examination showed that the cerebral cortex in all ACR treated animals exhibited fewer neurons and more condensed nuclei than normal cortex. A significant increase in apoptosis was found in the cerebral cortex of rat brains subjected to ACR treatment in a dose-dependent manner. The expression of TERT in the brain was significantly reduced by ACR treatment. The pro-apoptotic cleaved caspase-3 protein level was increased, while the anti-apoptotic Bcl-2 protein level was decreased by 30 - 50 mg/kg ACR. Our findings indicate that TERT and its downstream regulators of neuron apoptosis, including Bcl-2 and cleaved caspase-3, were involved in ACR neurotoxicity.
Polyacrylamide is used widely in industry, and its decomposition product, acrylamide (ACR), readily finds its way into commonly consumed cosmetics and baked and fried foods. ACR exerts potent neurotoxic effects in human and animal models. Telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase, traditionally has been considered to play an important role in maintaining telomere length. Emerging evidence has shown, however, that TERT plays an important role in neuroprotection by inhibiting apoptosis and excitotoxicity, and by promoting angiogenesis, neuronal survival and neurogenesis, which are closely related to the telomere-independent functions of TERT. We investigated whether and how the TERT pathway is involved in ACR induced neurotoxicity in rat cortical neurons. We found that ACR 1) significantly reduced the viability of cortical neurons as measured by MTT assay, 2) induced neuron apoptosis as revealed by FITC-conjugated Annexin V/PI double staining and flow cytometry (FACS) analysis, 3) elevated expression of cleaved caspase-3, and 4) decreased bcl-2 expression of cortical neurons. ACR also increased intracellular ROS levels in cortical neurons, increased MDA levels and reduced GSH, SOD and GSH-Px levels in mitochondria in a dose-dependent manner. We found that TERT expression in mitochondria was increased by ACR at concentrations of 2.5 and 5.0 mM, but TERT expression was decreased by 10 mM ACR. Telomerase activity, however, was undetectable in rat cortical neurons. Our results suggest that the TERT pathway is involved in ACR induced apoptosis of cortical neurons. TERT also may exert its neuroprotective role in a telomerase activity-independent way, especially in mitochondria.
Background. Prevention of complications is widely considered as the main aim of diabetes control. And diabetes education is the cornerstone for type 2 diabetes (T2D) management. However, traditional lecture-based diabetes patient education activities have small and shortlasting efficacy. Therefore, technology-based initiatives for diabetes patient education are urgently required. Objective. To evaluate Guessing, a popular game, as tool in increasing complication awareness of patients with newly diagnosed T2D during diabetes care. Patients and Methods. In a cohort study, 103 patients were split into Guessing Game group and control group. The opinions of patients and educators in Guessing Game group were surveyed. Patient performance was evaluated by test scores and the attendance to diabetes complication screening clinic. Results. A majority of patients and all educators believed that Guessing Game enhanced complication awareness. Educatees achieved higher total scores and test scores in "Fill in the Gaps" (one of 2 types of test item), more actively attended complication screening clinic, after using Guessing Game as an education tool. Conclusion. Guessing Game is an attractive and effective educational intervention to increase complication awareness of T2D patients.
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