Dobarro, M. (M.)

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    Efectos del propranolol sobre deterioro cognitivo y las patologías Amiloide y Tau en distintos modelos experimentales de enfermedad de Alzheimer
    (Servicio de Publicaciones de la Universidad de Navarra, 2015) Dobarro, M. (M.); Ramirez, M.J. (María Javier)
    Alzheimer's disease (AD) is the most common neurodegenerative disorder. AD is defined by progressive memory loss and cognitive impairments and at the molecular level by the presence of neurofibrillary tangles, composed of hyperphosphorylated Tau fibrils, and Aâ-containing amyloid plaques. Antihypertensive treatments have been associated with lower incidence of clinically diagnosed AD and better cognitive function, and it has been tested whether some antihypertensive drugs might influence AD through mechanisms independent of blood pressure-lowering activity. Propranolol, a â-adrenergic antagonist that is commonly used in the treatment of hypertension, shown experimentally to reverse cognitive deficits associated to stress and decrease of Aâ levels in vitro. In this work, we study the effect of propranolol in three animal models representing the three main groups of risk factors associated with the development of AD (age, genetics and environmental factors). After chronic treatment with propranolol at a lower dose than that used as antihypertensive (5 mg/kg), we evaluated the cognitive status of animals and different markers of AD in the hippocampus. In all cases, propranolol was able to reverse the increased levels of Aâ and hyperphosphorylated Tau. These effects may contribute to cognitive enhancement found in the three experimental models. In conclusion, propranolol seems to exert a protective role against disease neuropathology, making it a potential candidate for the treatment of AD.
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    Stress-induced anhedonia is associated to increased Alzheimer's disease markers
    (Wiley-Blackwell, 2012) Gagno, S. (S.); Aisa, B. (Bárbara); Ramirez, M.J. (María Javier); Solas, M. (Maite); Martisova, E. (Eva); Tordera, R.M. (Rosa María); Dobarro, M. (M.); Briones, A. (A.)
    Background and purpose: stress is believed to be associated with the development of neuropsychiatric disorders, including Alzheimer's disease (AD). We have studied mechanism implicated in vulnerability to stress and the relationship with changes in AD-related markers. Key results: when using the chronic mild stress (CMS) paradigm to induce anhedonia, 40% percent of rats were resistant to the development of anhedonia (CMSR), whereas the remaining were responsive (CMSA). Only CMSA rats displayed significant increases in immobility time in the forced swimming test, cognitive deficits in the novel object recognition test and significant decreases in synaptophysin, pAkt and pERK1/2 expression in the hippocampus. Increased levels of Aβ40, β-secretase (BACE1) and Tau phosphorylation were also found only in CMSA rats. Interestingly, all these effects in CMSA rats were reverted by normalization of the HPA axis activity by pharmacological treatment with the antidepressant venlafaxine. Conclusions and implications: It is proposed that vulnerability to stress might be related to development of AD pathology and that venlafaxine might be considered as a new therapeutical approach for the treatment of AD.