ABSTRACT
INTRODUCTION: In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. DEVELOPMENT: In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;<30% in macaques). The differences between normal and pathological (Alzheimer's) senility in these species are difficult to establish due to the lack of cognitive-behavioural studies in the many groups analysed, as well as the controversy in the results of these studies when they were carried out. However, in some macaques, a correlation between a high degree of functional brain impairment and a large number of neuropathological changes ("possible AD") has been found. CONCLUSIONS: In some non-human primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared.
Subject(s)
Alzheimer Disease/pathology , Primate Diseases/pathology , Primates , Animals , HumansABSTRACT
Introducción: Muchas publicaciones consideran que la enfermedad de Alzheimer (EA) es exclusivo de la especie humana, y que ningún otra especie animal sufre de la enfermedad. Sin embargo, diversos estudios han demostrado que algunas especies pueden presentar algunas de las características definitorias de la enfermedad humana, incluyendo tanto los cambios neuropatológicos y síntomas cognitivo-conductuales. Desarrollo: En este trabajo, los resultados publicados (PubMed) sobre cambios en el cerebro senil en los primates no humanos con diferentes grados de evolución, se revisan. Los cambios neuropatológicos asociados con la acumulación de amiloide o proteína tau fosforilada altamente son raras fuera del orden de los primates, pero en todos los sub-órdenes, familias, géneros y especies de primates no humanos que se han estudiado, algunos individuos seniles han demostrado amiloide acumulación en el cerebro. De hecho, en algunas especies la presencia de estos depósitos en la senilidad es constante. Cambios relacionados con la acumulación de la proteína tau son siempre de muy poca importancia, y se han detectado sólo en algunas especies de primates no humanos, tanto poco evolucionados y altamente evolucionada. En diferentes especies de primates no humanos, algunos tipos de cambios cognitivo-conductuales son más comunes en algunos individuos seniles en comparación con los individuos adultos normales y otras personas seniles de la especie. La importancia de determinar la longevidad de la especie en hábitats diferentes hábitats naturales, los hábitats nuevos, semi-cautividad, cautividad) se hace hincapié en estos estudios. Conclusiones: Las características morfológicas, histoquímicas y cognitivo-conductuales similares a los observados en los seres humanos de edad avanzada están presentes en seniles los primates no humanos. Además, otras características se observan en los primates no humanos podría ser indicativo de una patología «tipo Alzheimer» envejecimiento (AU)
Introduction: Many publications consider that Alzheimer's disease (AD) is exclusive to the human species, and that no other animal species suffers from the disease. However, various studies have shown that some species can present with some of the defining characteristics of the human disease, including both neuropathological changes and cognitive-behavioural symptoms. Development: In this work, the results published (PubMed) on senile brain changes in non-human primates of different degrees of evolution, are reviewed. The neuropathological changes associated with the accumulation of amyloid or highly phosphorylated tau protein are rare outside the primate order, but in all the sub-orders, families, genera and species of non-human primates that have been studied, some senile individuals have shown amyloid accumulation in the brain. In fact, in some species the presence of these deposits in senility is constant. Changes related to the accumulation of tau protein are always of very little significance, and have been detected only in some non-human primate species, both little evolved and highly evolved. In different species of non-human primates, some types of cognitive-behavioural changes are more common in some senile individuals when compared with both normal adult individuals and other senile individuals of the species. The importance of determining the longevity of the species in different habitats (natural habitats, new habitats, semi-captivity, captivity) is stressed in these studies. Conclusions: Morphological, histochemical and cognitive-behavioural features similar to those observed in elderly humans are present in senile non-human primates. Moreover, other characteristics seen in non-human primates could be indicative of a pathological «Alzheimer type» ageing (AU)
Subject(s)
Animals , Alzheimer Disease/veterinary , Primate Diseases/epidemiology , Aging/physiology , tau Proteins/analysis , Amyloid/analysis , Mental Disorders/epidemiology , Cognition Disorders/epidemiologyABSTRACT
INTRODUCTION: Many publications consider that Alzheimer's disease (AD) is exclusive to the human species, and that no other animal species suffers from the disease. However, various studies have shown that some species can present with some of the defining characteristics of the human disease, including both neuropathological changes and cognitive-behavioural symptoms. DEVELOPMENT: In this work, the results published (PubMed) on senile brain changes in non-human primates of different degrees of evolution, are reviewed. The neuropathological changes associated with the accumulation of amyloid or highly phosphorylated tau protein are rare outside the primate order, but in all the sub-orders, families, genera and species of non-human primates that have been studied, some senile individuals have shown amyloid accumulation in the brain. In fact, in some species the presence of these deposits in senility is constant. Changes related to the accumulation of tau protein are always of very little significance, and have been detected only in some non-human primate species, both little evolved and highly evolved. In different species of non-human primates, some types of cognitive-behavioural changes are more common in some senile individuals when compared with both normal adult individuals and other senile individuals of the species. The importance of determining the longevity of the species in different habitats (natural habitats, new habitats, semi-captivity, captivity) is stressed in these studies. CONCLUSIONS: Morphological, histochemical and cognitive-behavioural features similar to those observed in elderly humans are present in senile non-human primates. Moreover, other characteristics seen in non-human primates could be indicative of a pathological «Alzheimer type¼ ageing.
Subject(s)
Alzheimer Disease/pathology , Primates/physiology , Aged , Aging/physiology , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Amyloid beta-Peptides/metabolism , Animals , Behavior/physiology , Behavior, Animal/physiology , Brain/pathology , Cognition/physiology , Humans , Mice , Mice, Transgenic , tau Proteins/metabolismABSTRACT
Introducción. El cerebro adulto de mamíferos conserva la capacidad de generar nuevas neuronas a partir de células troncales/progenitoras neuronales. Las nuevas neuronas se integran a las redes preexistentes a través de un proceso denominado neurogénesis en el cerebro adulto, que está confinado a regiones del cerebro con un alto grado de plasticidad y asociadas a funciones que muestran deterioro en la enfermedad de Alzheimer. Desarrollo. A pesar de lo conocido, permanecen muchos interrogantes alrededor de estos fenómenos neurogénicos, su regulación y su potencial terapéutico real en neurodegeneraciones como la referida. Conclusiones. Hemos revisado el tema de la neurogénesis del cerebro adulto desde el punto de vista preclínico (modelado experimental) y terapéutico en el marco de la enfermedad de Alzheimer (AU)
Introduction. The adult brain of mammals preserves the capacity to generate new neurons from neural stem/ progenitor cells. The new neurons become part of the already-existing networks by means of a process called neurogenesis in the adult brain, which is restricted to regions of the brain with a high degree of plasticity and which are associated to functions that are impaired in Alzheimers disease. Development. Despite increasing knowledge, there are still many questions surrounding these neurogenic phenomena, their regulation and their real therapeutic potential in cases of neurodegeneration such as the one referred to here. Conclusions. We have reviewed the subject of neurogenesis of the adult brain from both the pre-clinical point of view (experimental modelling) and the therapeutic perspective within the framework of Alzheimers disease (AU)
Subject(s)
Humans , Neurogenesis/physiology , Alzheimer Disease/therapy , Stem Cell Transplantation , Cell- and Tissue-Based Therapy/methods , Hippocampus/physiopathology , Neurons/physiology , Disease Models, AnimalABSTRACT
INTRODUCTION: The adult brain of mammals preserves the capacity to generate new neurons from neural stem/progenitor cells. The new neurons become part of the already-existing networks by means of a process called 'neurogenesis in the adult brain', which is restricted to regions of the brain with a high degree of plasticity and which are associated to functions that are impaired in Alzheimer's disease. DEVELOPMENT: Despite increasing knowledge, there are still many questions surrounding these neurogenic phenomena, their regulation and their real therapeutic potential in cases of neurodegeneration such as the one referred to here. CONCLUSIONS: We have reviewed the subject of neurogenesis of the adult brain from both the pre-clinical point of view (experimental modelling) and the therapeutic perspective within the framework of Alzheimer's disease.
Subject(s)
Alzheimer Disease/therapy , Neurogenesis/physiology , Alzheimer Disease/physiopathology , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/physiology , Disease Models, Animal , Hippocampus/cytology , Humans , Neurons/physiology , Stem Cell Transplantation , Stem Cells/physiologyABSTRACT
Neurotrophins, like the nerve growth factor (NGF), trigger a variety of biological effects in their targets. Stimulating effects on antioxidant defenses have been postulated to underlie neurotrophic influence on neuron survival and maintenance. To test whether NGF is capable of inducing changes in glutathione-related enzymes in the aged cognitively impaired brain, glutathione reductase (GRD), glutathione S-transferase (GST) and total glutathione peroxidase (GPX) activities were measured in the striatum, septum, hippocampus and frontal cortex of four Sprague-Dawley rat groups: young (2 months old), aged (20 months old) untreated, aged cytochrome c-treated, and aged NGF-treated (icv delivery, 34 micrograms during 28 days). All the aged rats utilized in the study were memory impaired according to their performance in the Morris water maze test. These aged rats showed increases in the activities of septal and hippocampal GST, as well as, in the hippocampal, striatal and cortical GPX. These increases could be interpreted as compensatory responses to cope with the oxidative damage that has been accumulated by the aged brain. The increases in hippocampal and cortical GPX activity were attenuated by NGF treatment, whereas the neurotrophin induced an increase in GRD activity in the striatum of aged rats. These results point out GRD and GPX as possible targets of the neurotrophic effects.
