Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer’s Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice

Zhu, Yang; Huang, Hao; Chen, Zhi; Tao, Yong; Liao, Ling-Yi; Gao, Shi-Hao; Wang, Yanjiang; Gao, Ce

doi:10.1007/s12264-023-01098-7

Cited by 5 publications

(14 citation statements)

References 65 publications

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“…Moreover, siRNA-mediated ISCA1 knockdown eliminates the anti-Aβ effects of iTBS in AD model cells. 102 Therefore, we believe that improving mitochondrial function via targeting ISCA1 may be, at least partly, the potential mechanism by which iTBS reduces the Aβ load; because alterations in mitochondrial energy metabolism impact the balance of amyloidosis and nonamyloidosis pathways in APP metabolism. 138 Specifically, the inhibition of mitochondrial respiration can promote the amyloidosis process of APP, and consequently, induce the overproduction of Aβ.…”

Section: The Molecular Mechanism Of Rtms Treatment In Admentioning

confidence: 99%

“…129 Consistent with previous findings, we recently found that the rTMS FOR ALZHEIMER'S DISEASE | 25 number of activated microglia is reduced by iTBS treatment in the hippocampus and neocortex of APP/ PS1 mice, which is accompanied by a decrease in the release of pro-inflammatory factors, including IL-1β, IL-6, TNF-α, and IFN-γ. 85,101,102 In addition, Luo and colleagues reported that iTBS significantly decreases the type of M1 cells (pro-inflammatory microglia) and increases the type of M2 cells (anti-inflammatory microglia) via inhibiting TLR4/NFκB/NLRP3 signals in the infarcted area of transient MCAO-treated mice. 127 Notably, the application of a microglial inhibitor (PLX3397) abrogates iTBS-induced motor functional enhancement.…”

Section: The Cellular Mechanism Of Rtms Treatment In Admentioning

confidence: 99%

“…136,137 In our previous study, we reported that iTBS treatment could effectively modulate the mitochondrial functions in the brain of individuals with AD, including glucose uptake, oxidative stress, and mitochondrial dynamics. 102 Cell experiments showed that iron sulfur cluster assembly 1 (ISCA1), a crucial regulatory factor for mitochondrion, is involved in the mitochondrial modulation by iTBS treatment, 102 indicating that ISCA1 might be a target for iTBS therapy in AD. Moreover, siRNA-mediated ISCA1 knockdown eliminates the anti-Aβ effects of iTBS in AD model cells.…”

Section: The Molecular Mechanism Of Rtms Treatment In Admentioning

confidence: 99%

“…129 Previous studies suggest that rTMS could inhibit the activation of astrocytes in the brain of AD mice. 102,128 Moreover, rTMS facilitates the neuroprotection of primary astrocytes cultured in oxidative damaging conditions, 131 suggesting a direct action of rTMS on astrocytes. Astrocytes are also involved in synaptic remodeling because they are associated with the induction and maintenance of LTP and neuronal connectivity.…”

Section: The Cellular Mechanism Of Rtms Treatment In Admentioning

confidence: 99%

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Neuroprotective effects of repetitive transcranial magnetic stimulation on Alzheimer's disease: Undetermined therapeutic protocols and mechanisms

Zhu,

Liao,

Gao

et al. 2024

Neuroprotection

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Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by gradual deterioration of cognitive functions, for which an effective treatment is currently unavailable. Repetitive transcranial magnetic stimulation (rTMS), a well‐established noninvasive brain stimulation method, is utilized in clinical settings to address various neuropsychiatric conditions, such as depression, neuropathic pain, and poststroke dysfunction. Increasing evidence suggests that rTMS may enhance cognitive abilities in individuals with AD. However, its optimal therapeutic protocols and precise mechanisms are currently unknown, impeding its clinical implementation. In the present review, we aimed to summarize and discuss the efficacy‐related parameters in rTMS treatment, encompassing stimulus frequency, stimulus pattern, stimulus intensity, and the configuration of the stimulus coil. Furthermore, we reviewed promising rTMS therapeutic protocols involving various combinations of these factors, that were examined in clinical studies. Based on our analysis, we propose that a multisite high‐frequency rTMS (HF‐rTMS) regimen has value in AD therapy, and that promising single‐site protocols, such as HF‐rTMS, applied over the left dorsolateral prefrontal cortex, precuneus, or cerebellum are required to be validated in larger clinical studies. Lastly, we provide a comprehensive review of the potential mechanisms underlying the neuroprotective effects of rTMS on cognition in AD in terms of brain network modulation as well as cellular and molecular reactions. In conclusion, the interaction of diverse mechanisms may be responsible for the total therapeutic effect of rTMS on AD. This review provides theoretical and practical evidence for the future clinical application and scientific research of rTMS in AD.

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Section: The Molecular Mechanism Of Rtms Treatment In Admentioning

confidence: 99%

Section: The Cellular Mechanism Of Rtms Treatment In Admentioning

confidence: 99%

Section: The Molecular Mechanism Of Rtms Treatment In Admentioning

confidence: 99%

Section: The Cellular Mechanism Of Rtms Treatment In Admentioning

confidence: 99%

See 2 more Smart Citations

Neuroprotective effects of repetitive transcranial magnetic stimulation on Alzheimer's disease: Undetermined therapeutic protocols and mechanisms

Zhu,

Liao,

Gao

et al. 2024

Neuroprotection

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View full text Add to dashboard Cite

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“…The link between iron and the mitochondrial calcium uniporter may be relevant in other neurodegenerative conditions, including Alzheimer's disease [158][159][160]. Intermittent theta burst stimulation, which may improve cognition in Alzheimer's disease, was shown in APP/PS1 mice to increase the expression of iron-sulfur cluster assembly 1, which is needed for proper mitochondrial respiration [161].…”

Section: Reduced Connectivity and Iron Accumulationmentioning

confidence: 99%

Exploring Potential Mechanisms Accounting for Iron Accumulation in the Central Nervous System of Patients with Alzheimer’s Disease

LeVine

2024

Cells

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Elevated levels of iron occur in both cortical and subcortical regions of the CNS in patients with Alzheimer’s disease. This accumulation is present early in the disease process as well as in more advanced stages. The factors potentially accounting for this increase are numerous, including: (1) Cells increase their uptake of iron and reduce their export of iron, as iron becomes sequestered (trapped within the lysosome, bound to amyloid β or tau, etc.); (2) metabolic disturbances, such as insulin resistance and mitochondrial dysfunction, disrupt cellular iron homeostasis; (3) inflammation, glutamate excitotoxicity, or other pathological disturbances (loss of neuronal interconnections, soluble amyloid β, etc.) trigger cells to acquire iron; and (4) following neurodegeneration, iron becomes trapped within microglia. Some of these mechanisms are also present in other neurological disorders and can also begin early in the disease course, indicating that iron accumulation is a relatively common event in neurological conditions. In response to pathogenic processes, the directed cellular efforts that contribute to iron buildup reflect the importance of correcting a functional iron deficiency to support essential biochemical processes. In other words, cells prioritize correcting an insufficiency of available iron while tolerating deposited iron. An analysis of the mechanisms accounting for iron accumulation in Alzheimer’s disease, and in other relevant neurological conditions, is put forward.

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Progress of research and application of non-pharmacologic intervention in Alzheimer's disease

Tang,

Guo,

Guo

et al. 2024

Journal of Alzheimer’s Disease

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Alzheimer's disease (AD) is a common neurodegenerative disease characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles formed by high phosphorylation of tau protein. At present, drug therapy is the main strategy of AD treatment, but its effects are limited to delaying or alleviating AD. Recently, non-pharmacologic intervention has attracted more attention, and more studies have confirmed that non-pharmacologic intervention in AD can improve the patient's cognitive function and quality of life. This paper summarizes the current non-pharmacologic intervention in AD, to provide useful supplementary means for AD intervention.

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Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer’s Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice

Cited by 5 publications

References 65 publications

Neuroprotective effects of repetitive transcranial magnetic stimulation on Alzheimer's disease: Undetermined therapeutic protocols and mechanisms

Neuroprotective effects of repetitive transcranial magnetic stimulation on Alzheimer's disease: Undetermined therapeutic protocols and mechanisms

Exploring Potential Mechanisms Accounting for Iron Accumulation in the Central Nervous System of Patients with Alzheimer’s Disease

Progress of research and application of non-pharmacologic intervention in Alzheimer's disease

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