Long-term treadmill exercise improves spatial memory of male appswe/ps1de9 mice by regulation of bdnf expression and microglia activation

Xiong, Junwu; Li, Shicheng; Sun, Yongkun; Zhang, Xiaoshuang; Dong, Zhizhang; Zhong, Ping; Sun, Xiaoyan

doi:10.5604/20831862.1163692

Cited by 69 publications

(52 citation statements)

References 36 publications

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“…In a recent study, a 5-months long treadmill exercise increased levels of BDNF-positive cells and spatial memory in the APPswe/PS1dE9 AD mouse model (Xiong et al, 2015). Another study has also reported increase in BDNF and improved long-term potentiation following treadmill exercise in a rat model of AD (Aβ rats) (Dao et al, 2015).…”

Section: Modulating Bdnf Signaling In the Central Nervous Systemmentioning

confidence: 99%

Consequences of brain-derived neurotrophic factor withdrawal in CNS neurons and implications in disease

Mariga

Mitre

Chao

2017

Neurobiology of Disease

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Growth factor withdrawal has been studied across different species and has been shown to have dramatic consequences on cell survival. In the nervous system, withdrawal of nerve growth factor (NGF) from sympathetic and sensory neurons results in substantial neuronal cell death, signifying a requirement for NGF for the survival of neurons in the peripheral nervous system (PNS). In contrast to the PNS, withdrawal of central nervous system (CNS) enriched brain-derived neurotrophic factor (BDNF) has little effect on cell survival but is indispensible for synaptic plasticity. Given that most early events in neuropsychiatric disorders are marked by a loss of synapses, lack of BDNF may thus be an important part of a cascade of events that leads to neuronal degeneration. Here we review reports on the effects of BDNF withdrawal on CNS neurons and discuss the relevance of the loss in disease.

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Section: Modulating Bdnf Signaling In the Central Nervous Systemmentioning

confidence: 99%

Consequences of brain-derived neurotrophic factor withdrawal in CNS neurons and implications in disease

Mariga

Mitre

Chao

2017

Neurobiology of Disease

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“…We have recently shown that 6 months of voluntary running in 5xFAD mice did not result in any beneficial effects on soluble Aβ-levels, synaptic protein levels or cognitive behavior 24 . Interestingly, prior studies in other AD models suggest that exercise may reduce neuroinflammation by reducing microglial activation and levels of pro-inflammatory cytokines 31,32 . Because of its features, we view the 5xFAD model as suitable for studying the effects of exercise on neuroinflammatory and non-cognitive behavioral features of AD.…”

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confidence: 99%

Voluntary running does not reduce neuroinflammation or improve non-cognitive behavior in the 5xFAD mouse model of Alzheimer’s disease

Svensson

Andersson

Manouchehrian

et al. 2020

Sci Rep

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Physical exercise has been suggested to reduce the risk of developing Alzheimer's disease (AD) as well as ameliorate the progression of the disease. However, we recently published results from two large epidemiological studies showing no such beneficial effects on the development of AD. In addition, long-term, voluntary running in the 5xFAD mouse model of AD did not affect levels of soluble amyloid beta (Aβ), synaptic proteins or cognitive function. In this follow-up study, we investigate whether running could impact other pathological aspects of the disease, such as insoluble Aβ levels, the neuroinflammatory response and non-cognitive behavioral impairments. We investigated the effects of 24 weeks of voluntary wheel running in female 5xFAD mice (n = 30) starting at 2-3 months of age, before substantial extracellular plaque formation. Running mice developed hindlimb clasping earlier (p = 0.009) compared to sedentary controls. Further, running exacerbated the exploratory behavior in Elevated plus maze (p = 0.001) and anxiety in Open field (p = 0.024) tests. Additionally, microglia, cytokines and insoluble Aβ levels were not affected. Taken together, our findings suggest that voluntary wheel running is not a beneficial intervention to halt disease progression in 5xFAD mice.Alzheimer's disease (AD) is the most common form of dementia, affecting around 30 million people worldwide (WHO 2016). Even though cognitive dysfunction is a hallmark of AD, a majority of AD patients also suffer from other, non-cognitive symptoms such as depression and anxiety 1,2 . AD is characterized by accumulation of extracellular amyloid-beta (Aβ) plaques and progressive neurodegeneration. Further, the inflammatory response is also altered in the AD brain 3 . Postmortem studies using AD brains have revealed than pro-inflammatory cytokines, such as IL-1β and IL-6, accumulate around Aβ plaques 4,5 . In addition, microglial activation is increased 6 and correlates with the Aβ deposition 7,8 . Recently, a genome-wide association study revealed that genetics variants related to increased risk of developing AD are specifically enriched in enhancers of myeloid cells 9 . Interestingly, microglia are capable of phagocytosing Aβ aggregates and, thereby, facilitate Aβ clearance 10 . Contrastingly, neuronal Aβ production can induce cytokines in microglia and this can up-regulate the expression and enzymatic activity of β-secretase, thereby enhancing Aβ production 11 . Thus, it is likely that the microglial response in the AD brain contribute with both protective and harmful effects. Hence, future therapeutic interventions may focus on modulating different aspects of these responses.Several studies suggest that physical exercise is beneficial by reducing the risk of AD and slowing the progression of the pathology 12-14 . Exercise intervention may improve cognition 15,16 and ameliorate Aβ levels in patients 17 . Moreover, exercise was associated with larger gray matter volumes in cortex and hippocampus and improved cortical connectivity of cognitive netwo...

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“…Exercise was postulated to influence APP processing, because APP C-terminal fragments were reduced [84]. More recent studies in Tg2576 AD mice also found that exercise mitigated brain levels of Aβ 1–42 , and in APPswe/PS1dE9 mice, treadmill exercise was associated with improved spatial memory, more Brain-Derived Neurotrophic Factor (BDNF) positive cells and less activated microglia in the brain, but no change in brain Aβ [85, 86]. …”

Section: Mitochondrial Medicine and Alzheimer’s Diseasementioning

confidence: 99%

New Therapeutics to Modulate Mitochondrial Function in Neurodegenerative Disorders

Wilkins

Morris

2017

CPD

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Background Mitochondrial function and energy metabolism are impaired in neurodegenerative diseases. There is evidence for these functional declines both within the brain and systemically in Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. Due to these observations, therapeutics targeted to alter mitochondrial function and energy pathways are increasingly studied in pre-clinical and clinical settings. Methods The goal of this article was to review therapies with specific implications on mitochondrial energy metabolism published through May 2016 that have been tested for treatment of neurodegenerative diseases. Results We discuss implications for mitochondrial dysfunction in neurodegenerative diseases and how this drives new therapeutic initiatives. Conclusion: Thus far, treatments have achieved varying degrees of success. Further investigation into the mechanisms driving mitochondrial dysfunction and bioenergetic failure in neurodegenerative diseases is warranted.

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Long-term treadmill exercise improves spatial memory of male appswe/ps1de9 mice by regulation of bdnf expression and microglia activation

Cited by 69 publications

References 36 publications

Consequences of brain-derived neurotrophic factor withdrawal in CNS neurons and implications in disease

Consequences of brain-derived neurotrophic factor withdrawal in CNS neurons and implications in disease

Voluntary running does not reduce neuroinflammation or improve non-cognitive behavior in the 5xFAD mouse model of Alzheimer’s disease

New Therapeutics to Modulate Mitochondrial Function in Neurodegenerative Disorders

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