RESUMEN
The evidence for a protective role of physical activity on the risk and progression of Alzheimer's disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aß4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia.
Asunto(s)
Enfermedad de Alzheimer/complicaciones , Hipocampo/fisiopatología , Trastornos de la Memoria/complicaciones , Enfermedades Neurodegenerativas/complicaciones , Condicionamiento Físico Animal , Enfermedad de Alzheimer/fisiopatología , Animales , Modelos Animales de Enfermedad , Trastornos de la Memoria/fisiopatología , Ratones , Ratones Transgénicos , Enfermedades Neurodegenerativas/fisiopatología , Neuronas/fisiología , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVES: To determine the feasibility of visualization of the uvula and the soft palate during routine two-dimensional (2D) ultrasound examination and to develop a sonographic procedure that facilitates prenatal detection of isolated fetal cleft palate. METHODS: We examined 667 consecutive patients with a singleton pregnancy between 20 and 25 weeks of gestation who were referred to our practice for a detailed fetal anomaly scan. The uvula was visualized either in a frontal section through the neck and pharynx or via a transverse section with subsequent slight tilting of the transducer. The soft palate was visualized in a median sagittal section through the head. To test whether the techniques described are suitable for inclusion in routine examinations, the time allowed for a normal ultrasound scan was not changed from 30 min. RESULTS: A normal uvula could be visualized with a typical echo pattern (the 'equals sign') in 90.7% of the cases and the soft palate could be completely visualized in a median sagittal section in 85.3% of the cases. Visualization of at least one of the two structures (either the uvula or the soft palate) was successful in 98.4% of the cases. In one case an isolated cleft palate (in an otherwise normal fetus) was diagnosed; in one case with a cleft lip and palate, the cleft palate and the completely split uvula were detected. In 1.2% of the cases the examination did not provide sufficient information on either the uvula or the soft palate. CONCLUSIONS: In a high percentage of cases, relevant soft palate structures can be visualized successfully with 2D ultrasound, permitting cleft palate to be ruled out in routine examinations. Visualization of the equals sign proves an intact palate. Absence of the equals sign indicates cleft palate and should prompt further examination of the soft palate in a median sagittal section. Cleft palate can be confirmed when the soft palate cannot be visualized. This technique also facilitates evaluation of the soft palate in the event of a cleft lip and palate.