Telomere length and oxidative stress variations in a murine model of Alzheimer's disease progression.

Alzheimer's disease (AD) is the most common cause of dementia, and ageing is its major risk factor. Changes in telomere length have been associated with ageing and some degenerative diseases. Our aim was to explore some of the molecular changes caused by the progression of AD in a transgenic murine model (3xTg-AD; B6; 129-Psen1 Tg (APPSwe, tauP301L) 1Lfa). Telomere length was assessed by qPCR in both brain tissue and peripheral blood cells and compared between three age groups: 5, 9 and 13 months. In addition, a possible effect of oxidative stress on telomere length and AD progression was explored. Shorter telomeres were found in blood cells of older transgenic mice compared to younger and wild-type mice but no changes in telomere length in the hippocampus. An increase in oxidative stress with age was found for all strains, but no correlation was found between oxidative stress and shorter telomere length for transgenic mice. Telomere length and oxidative stress are affected by AD progression in the 3xTg-AD murine model. Changes in blood cells are more noticeable than changes in brain tissue, suggesting that systemic changes can be detected early in the disease in this murine model.

Citrulline supplementation improves spatial memory in a murine model for Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) correlates with the dysfunction of metabolic pathways that translates into neurological symptoms. An arginine deficiency, a precursor of nitric oxide (NO), has been reported for patients with AD. We aimed to evaluate the effect of citrulline oral supplementation on cognitive decline in an AD murine model. METHODS: Three-month citrulline or water supplementation was blindly given to male and female wild-type and 3 × Tg mice with AD trained and tested in the Morris water maze. Cerebrospinal fluid and brain tissue were collected. Ultra-performance liquid chromatography was used for arginine determinations and the Griess method for NO. RESULTS: Eight-month-old male 3 × Tg mice with AD supplemented with citrulline performed significantly better in the Morris water maze task. Arginine levels increased in the cerebrospinal fluid although no changes were seen in brain tissue and only a tendency of increase of NO was observed. CONCLUSIONS: Citrulline oral administration is a viable treatment for memory improvement in the early stages of AD, pointing to NO as a viable, efficient target for memory dysfunction in AD.

Oxidative stress in the elderly with diabetes mellitus or hypertension / Estrés oxidativo en adultos mayores con diabetes mellitus o hipertensión arterial

Background: Mexico City has the highest aging rate in the country, as well as a high prevalence of diabetes mellitus (DM) and hypertension (HT). It is known that each one of these conditions increase oxidative stress (OS) independently. Methods: With this study we described changes in OS of 18 patients without DM or HT (controls), 12 with DM, 23 with HT, and 18 with DM and HT, all of them members of the COSFAMM (Cohorte de Obesidad, Sarcopenia y Fragilidad en Adultos Mayores de México). OS was measured by the quantification of reactive oxygen species (ROS), by the oxidation of diclorofluorosceine, and by determination of lipid peroxidation by product malondialdehyde (MDA). Results: HT patients showed increased ROS levels, as did men with HT compared with the respective DM and HT groups. Also, women of control group showed higher levels of ROS compared with men. Conclusions: Generally, HT turned out to be the most influential factor for the increase of oxidative stress in the elderly while DM has no effect whatsoever.

Introducción: la Ciudad de México tiene el mayor índice de envejecimiento del país, así como una alta prevalencia de diabetes mellitus (DM) e hipertensión arterial (HTA). Se sabe que cada una de estas condiciones incrementa el estrés oxidativo (EO) de forma independiente. Métodos: en este estudio describimos los cambios en el EO de 18 pacientes sin DM ni HTA (controles), 12 con DM, 23 con HTA y 18 con DM y HTA, todos miembros de la Cohorte de Obesidad, Sarcopenia y Fragilidad en Adultos Mayores de México (COSFAMM). El EO fue medido por la cuantificación de especies reactivas de oxígeno (ERO) por la oxidación de la diclorofluorosceína (DCFH) y por determinación de peroxidación de lípidos por producto malondialdehído (MDA). Resultados: los pacientes con HTA mostraron niveles de ERO elevados, así como los hombres con HTA, comparados con los grupos correspondientes de DM y HTA. Asimismo, las mujeres del grupo control mostraron mayor cantidad de ERO que los hombres. Conclusiones: en general, la HTA en el adulto mayor resultó ser el factor que mayor contribución tiene en el incremento del estrés oxidativo, mientras que la DM no tiene efecto alguno.