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Infusion of Plasma from Exercised Mice Ameliorates Cognitive Dysfunction by Increasing Hippocampal Neuroplasticity
Tae-Woon Kim1,2, Sang-Seo Park2, Joon-Young Park3
1Exercise Rehabilitation Research Institute, Department of Exercise & Health Science, Sangmyung University, Seoul 03016, Korea.
Abstract:
Alzheimer's disease is the most common neurodegenerative brain disease causing dementia. It is characterized by slow onset and gradual worsening of memory and other cognitive functions. Recently, parabiosis and infusion of plasma from young mice have been proposed to have positive effects in aging and Alzheimer's disease. Therefore, this study examined whether infusion of plasma from exercised mice improved cognitive functions related to the hippocampus in a 3xTg-Alzheimer's disease (AD) model. We collected plasma from young mice that had exercised for 3 months and injected 100 µL of plasma into the tail vein of 12-month-old 3xTg-AD mice 10 times at 3-day intervals. We then analyzed spatial learning and memory, long-term memory, hippocampal GSK3β/tau proteins, synaptic proteins, mitochondrial function, apoptosis, and neurogenesis. In the hippocampus of 3xTg-AD mice, infusion of plasma from exercised mice improved neuroplasticity and mitochondrial function and suppressed apoptosis, ultimately improving cognitive function. However, there was no improvement in tau hyperphosphorylation. This study showed that plasma from exercised mice could have a protective effect on cognitive dysfunction and neural circuits associated with AD via a tau-independent mechanism involving elevated brain-derived neurotrophic factor due to exercise.
Insights
Plasma from exercised mice improved cognitive function in Alzheimer's disease models by enhancing neuroplasticity and mitochondrial function, independent of tau pathology. This suggests a novel therapeutic avenue for Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Gerontology
- Molecular Biology
Background:
- Alzheimer's disease (AD) is a leading cause of dementia, characterized by progressive cognitive decline.
- Parabiosis and young plasma infusion show potential benefits in aging and AD models.
- The impact of plasma from exercised mice on AD-related cognitive deficits requires investigation.
Purpose of the Study:
- To investigate the effects of plasma infusion from exercised mice on cognitive functions in a 3xTg-Alzheimer's disease mouse model.
- To explore the underlying mechanisms, including hippocampal neuroplasticity, mitochondrial function, apoptosis, and tau phosphorylation.
Main Methods:
- Collected plasma from young, exercising mice after 3 months of activity.
- Administered 100 µL of plasma via tail vein injection to 12-month-old 3xTg-AD mice, 10 times at 3-day intervals.
- Assessed cognitive functions (spatial learning, memory), hippocampal GSK3β/tau proteins, synaptic proteins, mitochondrial function, apoptosis, and neurogenesis.
Main Results:
- Plasma infusion improved spatial learning, memory, neuroplasticity, and mitochondrial function in the hippocampus of 3xTg-AD mice.
- Apoptosis was suppressed, and neurogenesis was enhanced, contributing to improved cognitive function.
- No significant improvement was observed in tau hyperphosphorylation, indicating a tau-independent mechanism.
Conclusions:
- Plasma from exercised mice exerts a protective effect on cognitive dysfunction and hippocampal neural circuits in an Alzheimer's disease model.
- The benefits appear to be mediated through a tau-independent pathway, potentially involving elevated brain-derived neurotrophic factor (BDNF).
- This study highlights exercise-derived plasma as a potential therapeutic strategy for Alzheimer's disease.
