Tesis doctoral de Fernando Guzman Sanchez
To date, the causes of alzheimer¿s disease (ad) have been not identified and there is still no consensus of opinion regarding the etiology of its sporadic form. Several genetic factors are known to be important, although they have been identified that account for a small number of cases of familial, early-onset ad. The majority of cases of ad, however, are sporadic and appear not to be associated with any known set of genetic markers. At present, only two factors are widely accepted as being related with the non-familial disease: the aging, and the possession of the apolipoproteine 4 allele (apoe ¿4). Additionally, women present a higher prevalence for the disease than men. This suggests that the disease has a multifactorial etiology, where the large majority of ad cases develop from an interaction of genetic and non-genetic factors. In the last years, the herpes simplex virus type 1 (hsv-1) has been related with the sporadic ad, and although a close correlation among apoe dosage, apoe ¿4 genotype and female gender with neuroinfection has been demonstrated, no aging studies have been evaluated to date. in the present work, it has been analyzed if the main risk factors related to ad (such as aging, oxidative damage, apoe presence, immunosuppression or female gender) are also correlated to the viral loads in the central nervous system (cns) of mice hematogenously infected with hsv-1. Secondly, the neuropathological consequences of the brain infection with aging were studied, by means the use of classical and non-invasive methodologies. The results obtained indicate that: (i) aging modulates the viral loads in cns, (ii) immune system influences the hsv-1 brain infection, (iii) apoe and female gender are correlated to brain virus levels, (iv) oxidative damage affects the brain infection, (v) hsv-1 infection induces neuroinflammation, astrogliosis and oxidative damage in the infected brains, (vi) magnetic resonance imaging and bioluminescence are valid methodologies for the in vivo study of hsv-1 infection, and (vii) hsv-1 infection in mice is related to cognitive impairment. in summarize, the experiments presented here clarify some points regarding the interaction of several risk factors related to ad, particularly regarding to the modulation of cerebral hsv-1 levels with aging, and with the neuropathological consequences of the brain infection. This work demonstrates that cerebral hsv-1 infection depends on the combination of aging, apoe profile, and gender in mice. The relationship among these parameters could be of great importance in the pathogenesis of the brain diseases associated to hsv-1 infection and particularly with ad.
Datos académicos de la tesis doctoral «Efectos neuropatológicos de la infección hematógena por el virus herpes simplex de tipo 1 en un modelo de envejecimiento en ratones.«
- Título de la tesis: Efectos neuropatológicos de la infección hematógena por el virus herpes simplex de tipo 1 en un modelo de envejecimiento en ratones.
- Autor: Fernando Guzman Sanchez
- Universidad: Autónoma de Madrid
- Fecha de lectura de la tesis: 26/11/2010
Dirección y tribunal
- Director de la tesis
- Fernando Valdivieso Amate
- Tribunal
- Presidente del tribunal: federico Mayor menendez
- Miguel Calero lara (vocal)
- Alberto Machado de la quintana (vocal)
- María trinidad Herrero ezquerro (vocal)