Effects of Pretreatment With Coenzyme Q10 (CoQ10) and High-Intensity Interval Training (HIIT) on FNDC5, Irisin, and BDNF Levels, and Amyloid-Beta (Aβ) Plaque Formation in the Hippocampus of Aβ-Induced Alzheimer's Disease Rats.

Physical exercise has been shown to protect against cognitive decline in Alzheimer's disease (AD), likely through the upregulation of brain-derived neurotrophic factor (BDNF). Recent studies have reported that exercise activates the FNDC5/irisin pathway in the hippocampus of mice, triggering a neuroprotective gene program that includes BDNF. This study aimed to investigate the effects of 8 weeks of pretreatment with coenzyme Q10 (CoQ10) and high-intensity interval training (HIIT), both individually and in combination, on FNDC5, irisin, BDNF, and amyloid-beta (Aβ) plaque formation in the hippocampus of Aβ-related AD rats. In this study, 72 male Wistar rats were randomly assigned to one of the following groups: control, sham, HIIT (low intensity: 3 min running at 50%-60% VO2max; high intensity: 4 min running at 85%-90% VO2max), Q10 (50 mg/kg, orally administered), Q10 + HIIT, AD, AD + HIIT, AD + Q10, and AD + Q10 + HIIT. Aβ injection resulted in a trend toward decreased levels of FNDC5, irisin, and BDNF, alongside increased Aβ plaque formation in the hippocampus of Aβ-induced AD rats. However, pretreatment with CoQ10, HIIT, or their combination significantly restored hippocampal levels of FNDC5, irisin, and BDNF, while also inhibiting Aβ plaque accumulation in these rats. Pretreatment with CoQ10 and HIIT improved the Aβ-induced reduction in BDNF levels probably through the FNDC5/irisin pathway and preventing Aβ plaque formation.

Puoyan-Majd S ，Parnow A ，Rashno M ，Heidarimoghadam R ，Komaki A ... -  《-》

The Protective Effects of High-Intensity Interval Training Combined with Q10 Supplementation on Learning and Memory Impairments in Male Rats with Amyloid-β-Induced Alzheimer's Disease.

Puoyan-Majd S ，Parnow A ，Rashno M ，Heidarimoghadam R ，Komaki A ... -  《-》

Effects of Aerobic Exercise and Resistance Training on Cognitive Function: Comparative Study Based on FNDC5/Irisin/BDNF Pathway.

Exercise has been recommended to suppress or prevent cognitive decline. Aerobic exercise (AE) may suppress cognitive decline via the fibronectin type III domain-containing protein 5 (FNDC5)/irisin/brain-derived neurotrophic factor (BDNF) pathway, and resistance training (RT) has a preventive effect on cognitive decline. However, the underlying mechanism remains unclear. This study verified the differences in the effects of AE and RT in suppressing and preventing cognitive decline based on the FNDC5/irisin/BDNF pathway. We divided senescence-accelerated mouse-prone 8 into three groups: control (CON), AE, and RT and evaluated their memory during exercise intervention through a novel object recognition (NOR) task. We quantified FNDC5/irisin, mBDNF, and TrkB in the hippocampus using enzyme-linked immunosorbent assay and FNDC5 in skeletal muscle using Western blotting (WB). Behavioral analysis using NOR showed that values for both AE and RT were significantly greater than those for CON. WB analysis showed that the peripheral FNDC5 expression in the skeletal muscle was increased in AE. The expression levels of FNDC5/irisin and mBDNF in the hippocampus were significantly increased in both AE and RT compared with that in CON but that if TrkB was increased only in AE. No significant difference was observed between AE and RT in the inhibitory effect on age-related cognitive decline, and both groups were effective. The FNDC5/Irisin/BDNF pathway, which was the focus of this experiment, may be specific to AE. The mechanism that suppresses cognitive decline may differ depending on the type of exercise.

Izawa S ，Nishii K ，Aizu N ，Kito T ，Iwata D ，Chihara T ，Sawada H ，Yao R ，Yamada K ... -  《-》

Treadmill exercise ameliorates hippocampal synaptic injury and recognition memory deficits by TREM2 in AD rat model.

The impairment of cognitive function has been associated with Alzheimer's disease (AD). Exercise exerts a positive modulatory effect on cognition by reducing synapse injury. However, limited in vivo evidence is available to validate the neuroprotective effect of TREM2 on synaptic function in this phenomenon. Here, we aim to explore whether physical exercise pretreatment alters Aβ-induced recognition memory impairment in structural synaptic plasticity within the hippocampus in AD rats. METHODS：: In study 1, fifty-two Sprague-Dawley (SD) rats were randomly divided into following four groups: control group (C group, n = 13), Alzheimer's disease group (AD group, n = 13), 4 weeks of physical exercise and Alzheimer's disease group (Exe+AD group, n = 13), 4 weeks of physical exercise and blank group (Exercise group, n = 13). Four weeks of treadmill exercise intervention was performed, and AD model were established by intra-cerebroventricular injection (ICV) injection of Aβ1-42 protein. After 3 weeks, we also conducted a novel object test to evaluate recognition memory in the behavior assessment. Golgi staining and transmission electron microscopy were used to evaluate the morphology and synaptic ultrastructure of neurons. Western blotting was used to measure the expression of hippocampal synaptic proteins. Extracellular neurotransmitters in the hippocampus were detected by microdialysis coupled with high-performance liquid chromatography. In study 2, 33 SD rats were randomly divided into three groups: 4 weeks of physical exercise and Alzheimer's disease group (Exe+AD group, n = 11), AAV-Control and physical exercise and Alzheimer's disease group (AAV-Control+Exe+AD group, n = 11), AAV-TREM2 and physical exercise and Alzheimer's disease group (AAV-TREM2 +Exe+AD group, n = 11). Stereotactic intracerebral injection in the bilateral hippocampus was performed to achieve microglial TREM2 down-expression by using adeno-associated virus (AAV) with CD68 promoter. After 4 weeks treadmill exercise and 3 weeks Aβ injection, all rats received behavior test and molecular experiment, which the same with experiment 2. Novel recognition index in novel object recognition test significantly decreased, and western blot demonstrate that hippocampal TREM2 protein is significantly decreased (P < 0.001). But physical exercise reversed this phenomenon(P < 0.001). In addition, compared with Con group, the neuron from Exe+AD group exhibited a more complex branching pattern (P < 0.05). And impaired synaptic ultrastructure was observed in AD group. Hippocampal synaptic-related protein (SYX, SYP, GAP43, PSD95) and neurotransmitter (DA, Glu, GABA) was also significantly decreased (P < 0.01) in AD group. But the neuroprotection effect can be found in Exe+AD group, which are associated with the inhibition of synaptic injury by activate hippocampal TREM2 (P < 0.05). However, when blockade of hippocampal TREM2 reduced brain protective effect of exercise in AD rat model, including increased the damage of neuronal dendritic complexity, synaptic ultrastructure, and the decrease of hippocampal synapses-related protein, typical neurotransmitter. Treadmill exercise facilitated recognition memory acquisition via TREM2-mediated structural synaptic plasticity of the hippocampus in an AD rat model.

Zhang L ，Liu Y ，Wang X ，Wu H ，Xie J ，Liu Y ... -  《-》

Voluntary running exercise promotes maturation differentiation and myelination of oligodendrocytes around Aβ plaques in the medial prefrontal cortex of APP/PS1 mice.

Previous studies have reported that running exercise could improves myelinization in hippocampus. However, the effects of running exercise on the differentiation and maturation of oligodendrocytes, and myelination surrounding Aβ plaques in the medial prefrontal cortex (mPFC) of the Alzheimer's disease (AD) brain have not been reported. Forty 10-month-old male APP/PS1 AD mice were randomly divided into the AD group and the AD running (AD+RUN) group, while 20 age-matched wild-type littermate mice were included in the WT group. The running group received three-month voluntary running exercise in a running cage, while the AD and WT groups were untreated. After the exercise intervention, all mice were given behavioral tests. The total number of mature oligodendrocytes (CC1+) in the mPFC of mice was precisely quantified using unbiased stereology. Myelin basic protein (MBP) and Aβ plaque, as well as the fluorescence area of MBP surrounding Aβ plaques, and the density and morphology of PDGFα+ cells in the mPFC were analyzed using immunofluorescence. The levels of working memory, cognitive memory, spatial learning and memory ability were decreased significantly in the AD group compared to the WT group, while these functions were significantly improved in the AD+RUN group compared to the AD group. The Aβ plaques in the mPFC were significantly reduced in the AD+RUN group compared to the AD group. The total number of CC1+ cells and the percentage of MBP fluorescence area surrounding Aβ plaques in the mPFC were significantly lower in the AD group compared to the WT group, but they were significantly higher in the AD+RUN group compared to the AD group. The density and branching complexity of PDGFα+ cells surrounding Aβ plaques in the mPFC were significantly higher in the AD group than in the WT group, while the AD+RUN group showed significantly lower density and branching complexity than the AD group. Changes in MBP expression around Aβ plaques, cell density and cell branching complexity of PDGFα+ cells around Aβ plaques were closely related to the number of Aβ plaques in mPFC, and they were also closely related to behavioral changes in mice. Voluntary running exercise could reduce Aβ plaque deposition and promote the maturation and myelination capacity of oligodendrocytes surrounding Aβ plaques in the mPFC of AD mice, thereby improving the learning and memory abilities of APP/PS1 transgenic AD mice.

Pan Q ，Jiang L ，Xiong Y ，Chao FL ，Liu S ，Zhang SS ，Zhu L ，Luo YM ，Xiao Q ，Tang J ，Liang X ，Tang Y ，Zhou CN ，Zhang L ... -  《-》