The effects of aging on neuronal morphology and on learning and memory in male mice.

摘要

The overall objective of this project was to investigate the effects of aging on the dendritic lengths, branch numbers, branch orders, average lengths per branch order, and spine densities on CA1 pyramidal neurons in behaviorally-characterized and non-behaviorally-characterized GFP-expressing male mice at 6, 18, and 24 months of age.;The first objective was to test the hypothesis that an increase in dendritic length, branch number, numbers of branch orders, and average lengths per branch order occurs with age in transgenic male mice expressing green fluorescent protein (GFP) in some neurons in the hippocampal formation. The results show that a decrease in apical dendritic length, branch number, number of branch orders, and average lengths per branch order occurs in middle-aged and old mice as compared to young adults. These data suggest an overall pruning and decrease in dendrite length with aging.;The second objective was to test the hypothesis that spine densities on CA1 pyramidal neurons decrease with age. The results show that no change in spine density occurs with age, which if viewed in isolation, would suggest synaptic number remains constant with age. However, these data in conjunction with the results showing that dendritic length decreases with age suggest that the overall number of synapses on CA1 pyramidal neurons decrease with age.;The third objective was to test the hypothesis that spatial learning and memory impairments in the Morris water maze (MWM) would occur in 18-month-old male, with more pronounced deficits observed at 24 months of age. In addition, it was hypothesized that aged animals with spatial-learning and memory impairments would have the same morphological characteristics hypothesized in the first and second objectives. The results showed that both 18- and 24-month-old mice have memory impairments, and that 24-month-old mice have learning and memory impairments more pronounced than those seen in the 18-month-olds. It was also observed the dendritic lengths, branch numbers, number of branch orders, and average lengths per branch order decreased on basal and distal apical dendrites in the older animals that were impaired, as compared to the younger animals that were not. Spine densities on basal dendrites in stratum oriens also decreased in the older learning and memory-impaired mice as compared to unimpaired young adults. These data show that impairments in learning and memory seem to correspond with decreases in dendritic length, branching patterns, and spine densities on basal dendrites.;The fourth objective was to test the hypothesis that the dendritic lengths do not change and spine densities increase on CA1 pyramidal neurons in mice trained and tested in the MWM as compared to controls. Training and testing resulted in a decrease in dendritic lengths and branch numbers in 6- and 24-month-old mice as compared to controls. Spine densities on distal apical dendrites in MWM trained and tested mice in stratum lacunosum-moleculare decreased in all three age groups as compared to controls. In addition, a decrease in spine density on dendrites in stratum radiatum was observed in 24-month-old trained and tested mice as compared to controls. Correlation analysis also showed that 6-month-old animals with a greater index of memory performance during probe trials had shorter dendritic lengths in distal apical dendrites of stratum lacunosum-moleculare. In contrast, 24-month-old male mice with a greater index of memory performance during probe trials had longer dendritic lengths in stratum-lacunosum moleculare. These data suggest that spatial learning tasks do affect CA1 pyramidal neuron morphology in specific ways depending on age group.