¿Existe la enfermedad de Alzheimer en todos los primates? Patología Alzheimer en primates no humanos y sus implicaciones fisiopatológicas (II) / Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)

Introducción: Existen algunas especies de primates no humanos con algunas de las caracteristicas definitorias de la enfermedad de Alzheimer (EA) del hombre, tanto en el aspecto neuropatologico como en el cognoscitivo-comportamental, y que son de importancia capital para entender y/o tratar esta enfermedad. Desarrollo: En esta segunda parte del estudio se analizan estas caracteristicas durante el proceso de envejecimiento en los modelos de EA mas importantes de primates no humanos no experimentales (lemur raton -Microcebus murinus-, cercopiteco verde -Chlorocebus aethiops- y los macacos Rhesus y de cola en tirabuzon -Macaca mulatta y M. arctioides-) y experimentales (modelos lesionales, neurotoxicos, farmacologicos, inmunologicos, etc.). En todos estos modelos se puede presentar neuropatologia amiloidea cerebral senil, aunque con diferente grado de incidencia (100% en cercopitecos; < 30% en macacos). Las diferencias entre senilidad normal y patologica (Alzheimer) en estas especies son dificiles de establecer por la falta de estudios cognoscitivo-comportamentales en muchos grupos analizados, asi como por la controversia existente en los resultados de estos estudios cuando se llevaron a cabo. Sin embargo, en algunos macacos se ha comprobado la correlacion entre un alto grado de deterioro funcional cerebral y una gran cantidad de alteraciones neuropatologicas (posible "Alzheimer"). Conclusiones: En los macacos, se puede considerar la existencia de un posible «continuum» entre proceso de envejecimiento "normal", "normal con no profundas alteraciones neuropatológicas y cognoscitivo-comportamentales", y "envejecimiento patologico" o "envejecimiento tipo Alzheimer". En otros casos, como el de los cercopitecos verdes, las alteraciones neuropatológicas son constantes y bastante marcadas, pero sus repercusiones cognoscitivo-comportamentales no parecen muy importantes. Ello hace suponer la posible existencia en la involucion senil fisiologica de una fase estable sin demencia aun cuando existan alteraciones neuropatológicas

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

Neurogénesis como diana terapéutica para la enfermedad de Alzheimer / Neurogenesis as a therapeutic target for Alzheimer's disease

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)

Effects of nerve growth factor on brain glutathione-related enzymes from aged rats

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 fraontal 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 æg 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 corical GPX activity were attenuated by NGF treatment, whereas the neurotrophin induced an increase in GRD activity in the striatum of aged rats. These resultas point out GRD and GPX as possible targets of the neurotrophic effects

Effects of nerve growth factor on brain glutathione-related enzymes from aged rats

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 fraontal 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 æg 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 corical GPX activity were attenuated by NGF treatment, whereas the neurotrophin induced an increase in GRD activity in the striatum of aged rats. These resultas point out GRD and GPX as possible targets of the neurotrophic effects