RESUMO
Impairments in motor coordination and cognition in normal and pathological aging are often accompanied by structural changes, that is, loss of synapses and neurons. Also, it has been shown recently that bone marrow stem cells can give origin to cells of different tissues, including neural cells. Given the therapeutic implications of increasing health and functional possibilities in the aged brain, we have tested the effects of rat femur bone marrow stem cells (rBMSCs) grafting to the striatum hippocampus of aged rats with motor or cognitive deficits, respectively. Bone marrow cells were transduced with an adenovirus driving the expression of green fluorescence protein (GFP) and other classic stains to determine their migration, engraftment, differentiation, and associated behavioral recovery. Five weeks after it, control and grafted rats were re-evaluated with the Morris Water Maze test, Passive avoidance, open-field, motor coordination, and Marshall tests and perfused. Brains were processed and analyzed for fluorescent protein expression. GFP was detected in cells with some differentiation degree into neural-like cells. Their exact phenotype is yet to be determined. A significant functional recovery was observed 6 weeks after grafting, suggesting a trophic interaction between rBMSCs and the aged/dystrophic host brain, or with the host brain progenitor cells and/or by increasing the number of functional cells at striatum or hippocampus, suggesting that the aging brain keeps its functional plasticity as well as that BMSCs are interesting candidates for cell replacement therapies in neurodegenerative disorders.
Assuntos
Envelhecimento , Células da Medula Óssea/citologia , Transplante de Medula Óssea , Corpo Estriado/patologia , Hipocampo/patologia , Memória , Células-Tronco/citologia , Animais , Diferenciação Celular , Proteínas de Fluorescência Verde , Proteínas Luminescentes/metabolismo , Masculino , Aprendizagem em Labirinto , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes de Fusão/metabolismoRESUMO
Aged (21 months) cognitively-impaired male Sprague Duwley rats received intraventricular infusion of nerve growth factor (NGF) or cytochrome C (Cit C) for 14 or 28 days using miniosmotic pumps and were evaluated either 1 week or 3 months after treatment. Groups of untreated young, aged-impaired and aged non-impaired rats were also evaluated. Under narcose recording and stimulating electrodes were stereotactically implanted in the dentate gyrus and the perforant path. The stimulation intensity was individually adjusted to obtain a half-maximal population spike (P) for test stimuli and a quarter-maximal for tetanization. The amplitude and latency of P and the slope (S) of the field EPSP were determinated before and at 2, 5, 15, 30 and 60 min after tetanization at 400 Hz. Paired stimuli at 30 ms inerval were also applied before and afeter tetanization. Aged, cognitively impaired rats showed an absent S potentiation and a delayed P potentiation, both in amplitude and latency, while non-impaired rats behaved like the young controls. Paired pulse inhibition showed no difference among groups before or after tetanization suggesting that the impaired potentiation is not due to an increased retroactive inhibition. NGF treatment ameliorates LTP deficits to levels equivalent to non-impaired rats, while Cit C controls showed no improvement. No differences appear among NGF treated groups, but evidence suggest that the animals evaluated 3 months after treatment developed a stronger potentiation
Assuntos
Animais , Envelhecimento , Potenciação de Longa Duração , Fatores de Crescimento Neural , Modelos Animais de DoençasRESUMO
Se expresa que los primates no humanos han sido estudiados extensivamente en relación con el patrón social y sexual, sin embargo, los mecanismos a través de los cuales la ontogenia ejerce su influencia sobre el uso de habitats, la locomoción y la adaptabilidad estructural permanecen aún sin resolver. Señala el interés en desarrollar modelos animales neurogerontológicos, para lo cual se desarrolla una base de datos en relación con la actividad motora espontánea, procesos congnoscitivos, estudios imagenológicos computarizados de cerebro, etc. para evaluar en primera instancia la sensibilidad de estos fenómenos funcionales al paso de la edad en babuinos y macacos