RESUMEN
According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases.
Asunto(s)
Envejecimiento/patología , Animales Domésticos , Animales de Laboratorio , Enfermedades de los Gatos/patología , Enfermedades de los Perros/patología , Enfermedades Neurodegenerativas/veterinaria , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/veterinaria , Animales , Encéfalo/patología , Gatos , Angiopatía Amiloide Cerebral/patología , Angiopatía Amiloide Cerebral/veterinaria , Modelos Animales de Enfermedad , Perros , Humanos , Enfermedades Neurodegenerativas/patología , Ovillos Neurofibrilares/patología , Placa Amiloide/patología , Placa Amiloide/veterinaria , Calidad de VidaRESUMEN
In geriatric dogs, Alzheimer-like behavior is frequently observed. This behavior has been classified by several authors using questionnaires and a correlation has been described between cognitive dysfunctions and Alzheimer-like pathology. In the present study, cognitive performance was correlated with brain pathology for 30 dogs of varying ages. Within these animals, two age-matched groups of old dogs with and without behavioral changes were compared. The behavioral changes were analyzed and scored with questionnaires and necropsy was performed to rule out any other cause for changed behavior. Measurements, (immuno)-histochemical staining and fluorescence microscopy were used to detect cortex atrophy, amyloid, rest-products of oxidative damage, demyelination and accumulations of macrophages in the brains of these dogs. Spearman rank correlation coefficients (r) were calculated and adjusted according to Bonferonni. In the whole group (young to very old dogs), the age of the animal showed a significant correlation with various behavioral changes (r = 0.7 to 0.9, P < 0.01). The dementia score correlated significantly (r = 0.6 to 0.8, P < 0.01) with all the brain lesions studied, except one, i.e. demyelination (r = -0.4, P > 0.05). These results suggest that a questionnaire can be used to diagnose Alzheimer-like changes in canine practice. Oxidative damage on a cellular and a nuclear level plays an important role in behavior changes.
Asunto(s)
Envejecimiento , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/veterinaria , Corteza Cerebral/patología , Trastornos del Conocimiento/etiología , 8-Hidroxi-2'-Desoxicoguanosina , Factores de Edad , Aldehídos/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Animales , Atrofia/metabolismo , Atrofia/patología , Conducta Animal , Corteza Cerebral/metabolismo , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/patología , Rojo Congo , Enfermedades Desmielinizantes/fisiopatología , Enfermedades Desmielinizantes/veterinaria , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animales de Enfermedad , Perros , Femenino , Inmunohistoquímica/métodos , Lipofuscina/metabolismo , Masculino , Estadísticas no ParamétricasRESUMEN
Senile plaques and cerebrovascular amyloidosis are major histopathological lesions in the brains of aged dogs. Different types of amyloid beta protein (A beta) positive plaques are known: diffuse ones and neuritic plaques. Diffuse plaques may contain membrane-bound A beta and/or small amounts of amyloid fibrils. Neuritic plaques are cored plaques with clusters of amyloid fibrils and degenerating neurities. In human amyloid plaques, a pathogenetic role for microglia cells has been described. The aim of this investigation was to study microglia cells in relationship to canine plaques and to investigate the localisation of amyloid plaques in relationship to vasculature. The lesions were studied by hematoxylin and eosin Congo red staining and immunohistochemistry with anti-A beta for plaques, with Mac 387, anti lysozyme and a series of lectins for mononuclear cells, with anti von Willebrand Factor and Lycopersicon esculentum (tomato) lectin for the endothelium of brain capillaries. Diffuse A beta-positive plaques were found in dogs of 10.8 years and older, and cored A beta-positive plaques with birefringent amyloid in Congo red-stained sections in subjects of 15 years and older. Accumulation of microglia cells in relationship to the plaques was not obvious. With anti A beta 8-17 the distribution of the plaques in the cortical layers varied. The younger dogs had primarily diffuse plaques in the deeper layers of the cortical grey matter. The older dogs showed more cored plaques than diffuse plaques which were found throughout all cortical grey matter layers. With anti A beta x-42 more plaques were found positive, especially diffuse ones, whereas staining results of anti A beta x-40 were more confined to amyloid plaques and vascular amyloid. A close spatial relationship was found between the cored plaques and capillaries.
Asunto(s)
Envejecimiento/metabolismo , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Macrófagos/metabolismo , Microglía/metabolismo , Placa Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Encéfalo/irrigación sanguínea , Capilares/metabolismo , PerrosRESUMEN
The pathogenesis of Alzheimer's disease is still unknown. In recent time oxidative stress has been discussed as an important contributor. In the present study we investigated the role of free radicals in the spontaneous canine model of Alzheimer's disease. We analysed end-products of lipid peroxidation: lipofuscin-like pigments (LFP), protein carbonyls, and vitamin E to obtain data on oxidative damage in brain of demented dogs. When the generation of free radicals is intensive the toxic products of lipid peroxidation can diffuse from the site of the primary formation and merge with erythrocytes. Therefore we also determined the level of lipid peroxidation in red blood cells. In brain of demented animals the level of LFP increased (to 247%, P<0.05) as well as of protein carbonyls (to 438%, P<0.01) while the vitamin E concentration was lowered (to 34%, P<0.01) when compared to age-matched non-demented controls. The end-products of lipid peroxidation have been found increased also in erythrocytes of demented dogs (250%, P<0.05). These results indicate intensive production of free radicals in brain of animals with dementia which induces damage to erythrocytes. Detection of the specific products of free radical damage in blood samples could be used for diagnostic purposes.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/veterinaria , Enfermedades de los Perros/metabolismo , Radicales Libres/metabolismo , Animales , Encéfalo/metabolismo , Perros , Eritrocitos/metabolismo , Peroxidación de Lípido , Lipofuscina/metabolismo , Estrés Oxidativo , Vitamina E/metabolismoRESUMEN
In the aging dog brain lesions develop spontaneously. They share some morphological characteristics with those of Alzheimer 's disease in man. Diffuse and primitive plaques are well known, whereas neuritic plaques rarely develop. Neurofibrillary tangles have not been seen in the canine. The aim of the present investigation was to study major age-related changes of the dog's brain using paraffin sections with respect to cross-immunoreactivity of tau, A beta protein and other immunoreactive components including hydroxynonenal protein, which is a marker for oxidative damage. The occurrence of neurofibrillary tangles and of the protein tau therein was studied in serial brain sections of two dogs with the Gallyas stain and by immunohistochemistry with three different antibodies against tau. Senile plaques were stained with a monoclonal anti-A beta (residues 8-17), polyclonal anti-apolipoprotein E and a monoclonal antibody against 4-hydroxynonenal (HNE). Amyloid deposits and controls were screened by Congo red staining viewed in fluorescent light, followed by polarized light for green birefringence. With the Gallyas stain and one of the antisera against tau, neurofibrillary tangles were revealed in a similar dispersed pattern, whereas the other antitau antisera gave negative results. With the anti-HNE a positive reaction was found in cerebral amyloid deposits and in vascular wall areas where amyloid deposition was confirmed by Congo-red staining, and in perivascular cells and in some neurons. These results indicate that the canine with his tangles and plaques which show oxidative changes, forms a spontaneous modelfor understanding the early changes and their interrelationships in Alzheimer's disease.