Amyloid Tau Sildenafil SAMP8 Aging Materias Investigacion::Farmacia::Farmacia y farmacología
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Orejana, L. ""Estudio de las principales vías responsables del efecto terapéutico del sildenafilo sobre el deterioro cognitivo del ratón de senescencia acelerada SAMP8"". Aguirre, N. (dir); Puerta, E. (codir.). Tesis doctoral. Universidad de Navarra, Pamplona, 2012
Aging is associated with a deterioration of cognitive performance particularly of learning and memory and with increased risk of neurodegenerative disorders. Undoubtedly, identifying the key markers and how they interact to turn benign aging into pathologic seems a crucial step for the development of therapeutic strategies to prevent or hinder the progression of aging and neurodegenerative diseases.
The senescence-accelerated mouse (SAM) is comprised of 14 strains derived from selective inbreeding of the AKR/J strain. One of these substrains, the senescence-accelerated mouse prone-8 (SAMP8) strain manifests irreversible advancing senescence and shares similar characteristics with aged humans. Interestingly, SAMP8 mice also exhibit age-related learning and memory deficits, increased expression of hyperphosphorylated tau as well as amyloid-like deposits in the brain. Given such features, SAMP8 mice have been proposed as one plausible age-associated Alzheimer¿s disease (AD) animal model and a suitable rodent model for studying the molecular mechanisms underlying cognitive impairment in aged subjects.
Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor initially approved for the treatment of erectile dysfunction and nowadays also for pulmonary arterial hypertension. Several studies have shown that sildenafil improves memory in rats and mice. Moreover, recent investigations have demonstrated that sildenafil also restores the cognitive function in a transgenic mouse model of AD.
Based on these premises, the aim of the present work was to explore whether sildenafil could reverse the memory impairments shown by SAMP8 mice as well as the underlying mechanisms. In particular, we focused our study on the effects of sildenafil on tau and amyloid pathology, the two main histopatological hallmarks of Alzheimer's disease.