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.

Chemotherapy is associated with the side effects including damage to the mitochondrial DNA. Doxorubicin (DOX) serves as a chemotherapeutic agent for the patients with breast cancer or prostate cancer. DOX causes muscle weakness and fatigue. We investigated the effects of treadmill exercise on DOX-induced apoptosis and mitochondrial dysfunction in relation to central fatigue. For this study, we used the rat model of DOX-induced muscle damage. DOX (2 mg/kg) was intraperitoneally injected 1 time per week for 4 weeks. Treadmill running continued 5 days per week for 4 weeks. Muscle strength and fatigue index in the gastrocnemius were measured. Immunohistochemistry for the expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe was conducted. We used western blot analysis for the expressions of Bax, Bcl-2, and caspases-3 in the gastrocnemius. Mitochondrial function in the gastrocnemius was also evaluated. DOX treatment decreased muscle strength with increase of fatigue index in the gastrocnemius. Mitochondria function was deteriorated and apoptosis in the gastrocnemius was enhanced by DOX treatment. Expressions of TPH and 5-HT in the dorsal raphe were increased by DOX treatment. Treadmill exercise attenuated DOX-induced muscle fatigue and impairment of mitochondria function. Apoptosis in the gastrocnemius was inhibited and over-expression of TPH and 5-HT was suppressed by treadmill exercise. Apoptosis was enhanced and mitochondria function was deteriorated by DOX treatment, resulting in muscle weakness and central fatigue. Treadmill exercise suppressed apoptosis and prevented deterioration of mitochondria function in muscle, resulting in alleviation of muscle weakness and central fatigue during DOX therapy.

Purpose: Hyperlipidemia, which promotes the development of atherosclerosis, ischemic stroke, and other forms of brain injury, can be induced by poloxamer-407. Berberine is a primary pharmacological active component of Coptidis Rhizoma that has a number of therapeutic activities. This study investigated the effects of berberine on poloxamer-407-induced brain inflammation by evaluating its effects on short-term memory, cell proliferation, inflammation, and apoptosis in the hippocampus. Methods: To induce hyperlipidemia in a rat model, 500 mg/kg of poloxamer-407 was injected intraperitoneally. Berberine was orally administered to the rats in the berberine-treated groups once a day for 4 weeks. The step-down task avoidance task was performed to measure short-term memory. An analysis of serum lipids, immunohistochemistry for 5-bromo-2′-deoxyuridine, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1) in the dentate gyrus, and western blot analysis for Bax, Bcl-2, and cytochrome c in the hippocampus were performed. Results: In hyperlipidemic rats, berberine reduced the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol and increased the level of high-density lipoprotein cholesterol in hyperlipidemic rats. Berberine also increased cell proliferation and short-term memory, as well as decreasing the expression of GFAP, Iba1, Bax, and cytochrome c and increasing Bcl-2 expression. Conclusions: Berberine treatment improved short-term memory in hyperlipidemia by increasing neuronal proliferation and inhibiting neuronal apoptosis. Berberine treatment also improved lipid metabolism.

Advanced maternal age (AMA) denotes an age of ≥35 years during the time of delivery. Maternal metabolism affects the offspring’s physical and neurological development as well as their cognitive function. This study aimed to elucidate the effects of exercise training among old female animals on the cognitive function, hippocampal neuroplasticity, mitochondrial function, and apoptosis in the offspring. We found that the offspring of mothers with AMA without exercise training had decreased spatial learning and memory, brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95) protein levels, neurogenesis, and mitochondrial function, as well as hippocampal cell death. Contrastingly, offspring of mothers with AMA with exercise training showed improved spatial learning, memory, hippocampal neuroplasticity, and mitochondrial function. These findings indicate that despite the AMA, increasing fitness through exercise significantly contributes to a positive prenatal environment for fetuses. The maternal exercises augmented the hippocampal levels of BDNF, which prevents decreased cognitive function in the offspring of mothers with AMA.

For humans, maternal old age means the age of 35 or older at the time of childbirth. Maternal metabolism not only affects the cognitive func-tion of the offspring, but also affects their physical and neurological de-velopment. This study aims to elucidate the effects of exercise training on spatial learning memory, neurogenesis, and apoptosis in the off-spring of old mice. Using mice, the offspring of old mothers showed im-paired spatial learning memory, decreased brain-derived neurotrophic factor and postsynaptic density protein 95 levels, suppressed neuro-genesis, and increased hippocampal apoptotic cell death. In contrast, the offspring of the old mothers had improved spatial learning memory, increased brain-derived neurotrophic factor and postsynaptic density protein 95 levels, increased neurogenesis, and decreased hippocampal apoptotic cell death when they received exercise training. The present results indicate that there is apparent spatial learning memory impair-ment among the offspring of old mothers, but by contrast, exercise can ameliorate spatial learning memory impairment. Exercise can be an ef-fective countermeasure against memory decline in the offspring of old mothers.