ABSTRACT
Many studies have shown that estrogen replacement therapy (ERT) can improve cognitive function and affect the structure of the brain, including the white matter, in postmenopausal women. However, it is unclear whether ERT plays an important role in white matter remodeling in postmenopausal women. In the present study, middle-aged (9-12-month-old) female Sprague-Dawley rats were bilaterally ovariectomized (OVX) and randomly allocated to the vehicle treatment (OVX+Veh) group or the 17ß-estradiol replacement (OVX+E) group. After 1 month of treatment, spatial learning and memory capacities were assessed using the Morris water maze task. Then, stereological methods were used to quantitatively evaluate white matter volume and myelinated fiber parameters of the white matter in the 2 groups of rats. The results revealed that the mean escape latency of the OVX+E rats in the Morris water maze task was significantly shorter than that of the OVX+Veh rats. The volume density of the myelinated fibers and the volume density and total volume of the myelin sheaths were significantly greater in the OVX+E rats than in the OVX+Veh rats. However, there were no significant differences in white matter volume or in the total length or volume of myelinated fibers in white matter between the 2 groups of rats. Our results showed that 1 month of ERT had significant beneficial effects on spatial learning capacity and on the myelin sheaths and myelinated fibers in the white matter of middle-aged OVX rats.
Subject(s)
Estradiol/administration & dosage , Estradiol/pharmacology , Estrogen Replacement Therapy , Myelin Sheath/pathology , Ovariectomy , White Matter/pathology , Animals , Female , Humans , Maze Learning/drug effects , Memory/drug effects , Postmenopause , Rats, Sprague-Dawley , Spatial Learning/drug effectsABSTRACT
Alzheimer's disease (AD), the most common cause of dementia in the elderly, is characterized by deficits in cognition and memory. Although amyloid-ß (Aß) accumulation is known to be the earliest pathological event that triggers subsequent neurodegeneration, how Aß accumulation causes behavioral deficits remains incompletely understood. In this study, using the Morris water maze test, ELISA and stereological methods, we examined spatial learning and memory performance, the soluble Aß concentration and the myelination of fibers in the hippocampus of 4-, 6-, 8- and 10-month-old Tg2576 AD model mice. Our results showed that spatial learning and memory performance was significantly impaired in the Tg2576 mice compared to the wild type (WT) controls and that the myelinated fiber length in the hippocampal dentate gyrus (DG) was markedly decreased from 0.33 ± 0.03 km in the WT controls to 0.17 ± 0.02 km in the Tg2576 mice at 10 months of age. However, the concentrations of soluble Aß40 and Aß42 were significantly increased as early as 4-6 months of age. The decreased myelinated fiber length in the DG may contribute to the spatial learning and memory deficits of Tg2576 mice. Therefore, we suggest that the significant accumulation of soluble Aß may serve as a preclinical biomarker for AD diagnosis and that protecting myelinated fibers may represent a novel strategy for delaying the progression of early-stage AD.
Subject(s)
Alzheimer Disease/pathology , Dentate Gyrus/pathology , Nerve Fibers, Myelinated/pathology , Aging/pathology , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Dentate Gyrus/metabolism , Disease Models, Animal , Humans , Male , Maze Learning , Memory , Mice, Transgenic , Nerve Fibers, Myelinated/metabolism , Organ Size , Peptide Fragments/metabolism , Random AllocationABSTRACT
To investigate the effect of running exercise on myelinated fibers in the dentate gyrus (DG) of the hippocampus during Alzheimer's disease (AD), 6-month-old male APP/PS1 transgenic mice were randomly assigned to control or running groups. The running group mice were subjected to a running protocol for four months. The behaviors of the mice from both group mice were then assessed using the Morris water maze, and the total volume of the DG and the related quantitative parameters with characteristics of the myelinated nerve fiber and the myelin sheath in the DG were investigated using unbiased stereological techniques and electron microscopy. Learning and spatial memory performances were both significantly increased in the running group compared with the control group. There was no significant difference in the gratio of the myelinated axons between the two groups. However, the DG volume, the myelinated fiber length and volume in the DG, and the myelin sheath volume and thickness in the DG were all significantly increased in the running group mice compared with the control group mice. These results indicated that running exercise was able to prevent DG atrophy and delay the progression of the myelinated fiber loss and the demyelination of the myelin sheaths in the DG in an AD mouse model, which may underlie the running-induced improvement in learning and spatial memory. Taken together, these results demonstrated that running exercise could delay the progression of AD.
