Protective Effects of 17ß-Estradiol on Hippocampal Myelinated Fibers in Ovariectomized Middle-aged Rats.

Estrogen replacement therapy (ERT) improves hippocampus-dependent cognition. This study investigated the impact of estrogen on hippocampal volume, CA1 subfield volume and myelinated fibers in the CA1 subfield of middle-aged ovariectomized rats. Ten-month-old bilaterally ovariectomized (OVX) female rats were randomly divided into OVX + E2 and OVX + Veh groups. After four weeks of subcutaneous injection with 17ß-estradiol or a placebo, the OVX + E2 rats exhibited significantly short mean escape latency in a spatial learning task than that in the OVX + Veh rats. Using stereological methods, we did not observe significant differences in the volumes of the hippocampus and CA1 subfields between the two groups. However, using stereological methods and electron microscopy techniques, the total length of myelinated fibers and the total volumes of myelinated fibers, myelin sheaths and myelinated axons in the CA1 subfields of OVX + E2 rats were significantly 38.1%, 34.2%, 36.1% and 32.5%, respectively, higher than those in the OVX + Veh rats. After the parameters were calculated according to different diameter ranges, the estrogen replacement-induced remodeling of myelinated fibers in CA1 was mainly manifested in the myelinated fibers with a diameter of <1.0 µm. Therefore, four weeks of continuous E2 replacement improved the spatial learning capabilities of middle-aged ovariectomized rats. The E2 replacement-induced protection of spatial learning abilities might be associated with the beneficial effects of estrogen on myelinated fibers, particularly those with the diameters less than 1.0 µm, in the hippocampal CA1 region of middle-aged ovariectomized rats.

Running exercise protects against myelin breakdown in the absence of neurogenesis in the hippocampus of AD mice.

Neurogenesis might influence oligodendrogenesis and selectively instruct myelination in the mammalian brain. Running exercise could induce neurogenesis and protect the myelin sheaths in the dentate gyrus of AD mice. It is unclear whether running exercise can protect myelin sheaths in the absence of neurogenesis in the hippocampus of AD mice. Six-month-old male APP/PS1 transgenic mice were randomly assigned to a control group (Tg control) or a running group (Tg runner), and age-matched non-transgenic littermates were used as a wild-type group (WT control). The Tg runner mice were subjected to a running protocol for four months. The behaviors of the mice in the three groups were then assessed using the Morris water maze, and related quantitative parameters of the myelin sheaths within the CA1 field were investigated using unbiased stereological and electron microscopy techniques. Learning and spatial memory performance, CA1 volume, the volumes of the myelinated fibers, and myelin sheaths in the CA1 field were all significantly worse in the Tg control mice than in the WT control mice. Learning and spatial memory performance, CA1 volume and the volume of the myelin sheaths in the CA1 field were all significantly greater in the Tg runner mice than in the Tg control mice. These results reveal demyelinating lesions in the CA1 field of Alzheimer's disease (AD) mice and indicate that running exercise could protect against myelin sheath degeneration in the absence of neurogenesis, thereby reducing CA1 atrophy and delaying the onset and progression of AD.

Effects of estrogen replacement therapy on the myelin sheath ultrastructure of myelinated fibers in the white matter of middle-aged ovariectomized rats.

The effects of estrogen replacement therapy (ORT) on white matter and the myelin sheath ultrastructure in the white matter of middle-aged ovariectomized (OVX) rats were investigated in this study. Middle-aged rats were ovariectomized and divided into a placebo replacement (OVX + O) group and an estrogen replacement (OVX + E) group. Then, the Morris water maze, electron microscope techniques, and stereological methods were used to investigate the effects of ORT on spatial learning capacity, white matter volume and the myelin sheath ultrastructure in the white matter. We found that the spatial learning capacity of the OVX + E rats was significantly improved compared with that of the OVX + O rats. When compared with that of OVX + O rats, the total volume of the myelin sheaths in the white matter of the OVX + E rats was significantly increased by 27%, and the difference between the outer perimeter and inner perimeter of the myelin sheaths of the white matter in the OVX + E rats increased significantly by 12.6%. The myelinated fibers with mean diameters of 1.2-1.4 µm were significantly longer (46.1%) in the OVX + E rats; the difference between the mean diameter of myelinated fibers and the mean diameter of axons (0-0.4 µm) was significantly increased by 21.6% in the OVX + E rats. These results suggested that ORT had positive protective effects on the spatial learning ability and on the myelin sheath ultrastructure in the white matter of middle-aged OVX rats.

Exercise Prevents Cognitive Function Decline and Demyelination in the White Matter of APP/PS1 Transgenic AD Mice.

BACKGROUND: Whether exercise could delay the cognitive function decline and structural changes in Alzheimer's disease (AD) are not fully understood. METHODS: 6-month-old male APP/PS1 double transgenic mice ran four months and then the effects of exercise on the cognitive function and the white matter of AD were investigated. RESULTS: The mean escape latency of the excercised group was significantly shortened when compared to that of the sedentary group. The percentage of time in target quadrant and the target zone frequency of the exercised group were significantly increased when compared to the sedentary group. The white matter volume, the myelinated fiber volume and axon volume in the white matter of the exercised group were significantly increased when compared to the sedentary group. CONCLUSION: Exercise could improve the cognitive function in AD, and the effects of exercise on the white matter of AD might be one of the structural bases for the protective effect of exercise on the cognitive function of AD. The exercise-induced protection of the white matter in AD might be due to the fact that the exercise prevented the demyelination of the myelinated fibers in the white matter of AD.

17ß-estradiol replacement therapy protects myelin sheaths in the white matter of middle-aged female ovariectomized rats: a stereological study.

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.

Running Exercise Reduces Myelinated Fiber Loss in the Dentate Gyrus of the Hippocampus in APP/PS1 Transgenic Mice.

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.