Efectos de la Estimulación Cognitiva en la Enfermedad de Alzheimer: Implicación de BDNF
Palabras clave : 
Materias Investigacion::Ciencias de la Salud
Neurobiología molecular
Fecha de publicación: 
abr-2013
Fecha de la defensa: 
13-jun-2013
Cita: 
GUEREÑU LOPETEGI, Gorka. “Efectos de la Estimulación Cognitiva en la Enfermedad de Alzheimer: Implicación de BDNF”. Gil Bea, Francisco Javier y Ramírez, María Javier (dir.). Tesis doctoral. Universidad de Navarra, Pamplona, 2013
Resumen
Education and cognitive occupations is commonly associated to reduced risk of Alzheimer¿s disease (AD) dementia. Animal studies have demonstrated that cognitive stimulation (CS) achieved by social/physical activities and/or enriched environments compensates for memory decline. We have elaborated a novel paradigm of CS that is devoid of physical/social activity and enriched environments. 4 months-old Tg2576 mice were cognitively trained for 8 weeks and, after a break of 8 months, long-lasting effects of CS on cognitive abilities and AD-like pathology were measured. MWM and NOR tests showed that deficits in spatial and recognition memories were compensated by CS. These outcomes were accompanied by increased levels of hippocampal post-synaptic markers (PSD95 and NR1) and proteins involved in synaptic formation (Arc, â-catenin). CS softened amyloid pathology in terms of reduced levels of Aâ1-42 and the dodecameric assembly, referred as Aâ*56. CS appeared to affect the APP processing since differences in levels of ADAM17, BACE1 and C99/C83 ratio were found. Tau hyper-phosphorylation and high activities of Tau kinases were also reduced by CS. In contrast, CS did not induce any of these molecular changes in wild-type mice. The present findings suggest beneficial and long-lasting effects of CS early in life on cognitive decline and AD-like pathology. In this research work we have also characterized the role of BDNF on a new mechanism by which cognitive stimulation exerts its beneficial effects on cognitive decline and AD-like pathology.

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TESIS GORKA GEREÑU LOPETEGI.pdf
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4,01 MB
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