Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage

Han, Wen; Luo, Yinpei; Li, Zhi; Yang, Xiu-Fang; Wu, Xiaoying; Tian, Xiaobin

doi:10.4103/1673-5374.337053

Neural Regen Res

2022

DOI: 10.4103/1673-5374.337053

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Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage

Wen Han

Yinpei Luo

Zhi Li

et al.

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Cited by 6 publications

References 74 publications

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Advancement in modulation of brain extracellular space and unlocking its potential for intervention of neurological diseases

Yong,

Cai,

Lin

et al. 2024

Med-X

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Cells in the brain are surrounded by extracellular space (ECS), which forms porous nets and interconnected routes for molecule transportation. Our view of brain ECS has changed from a largely static compartment to dynamic and diverse structures that actively regulate neural activity and brain states. Emerging evidence supports that dysregulation of brain ECS contributes to the pathogenesis and development of many neurological disorders, highlighting the importance of therapeutic modulation of brain ECS function. Here, we aim to provide an overview of the regulation and dysfunction of ECS in healthy and pathological brains, as well as advanced tools to investigate properties of brain ECS. This review emphasizes modulation methods to manipulate ECS with implications to restore their function in brain diseases. Graphical Abstract

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Advancement in modulation of brain extracellular space and unlocking its potential for intervention of neurological diseases

Yong,

Cai,

Lin

et al. 2024

Med-X

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Contralesional Anodal Transcranial Direct Current Stimulation Promotes Intact Corticospinal Tract Axonal Sprouting and Functional Recovery After Traumatic Brain Injury in Mice

Chen,

Tan,

Zhang

et al. 2024

Neurorehabil Neural Repair

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Background Anodal transcranial direct current stimulation (AtDCS), a neuromodulatory technique, has been applied to treat traumatic brain injury (TBI) in patients and was reported to promote functional improvement. We evaluated the effect of contralesional AtDCS on axonal sprouting of the intact corticospinal tract (CST) and the underlying mechanism in a TBI mouse model to provide more preclinical evidence for the use of AtDCS to treat TBI. Methods TBI was induced in mice by a contusion device. Then, the mice were subjected to contralesional AtDCS 5 days per week followed by a 2-day interval for 7 weeks. After AtDCS, motor function was evaluated by the irregular ladder walking, narrow beam walking, and open field tests. CST sprouting was assessed by anterograde and retrograde labeling of corticospinal neurons (CSNs), and the effect of AtDCS was further validated by pharmacogenetic inhibition of axonal sprouting using clozapine-N-oxide (CNO). Results TBI resulted in damage to the ipsilesional cortex, while the contralesional CST remained intact. AtDCS improved the skilled motor functions of the impaired hindlimb in TBI mice by promoting CST axon sprouting, specifically from the intact hemicord to the denervated hemicord. Furthermore, electrical stimulation of CSNs significantly increased the excitability of neurons and thus activated the mechanistic target of rapamycin (mTOR) pathway. Conclusions Contralesional AtDCS improved skilled motor following TBI, partly by promoting axonal sprouting through increased neuronal activity and thus activation of the mTOR pathway.

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Blockade of adenosine A2A receptors reverses early spatial memory defects in the APP/PS1 mouse model of Alzheimer’s disease by promoting synaptic plasticity of adult-born granule cells

Ji,

Yang,

Xiong

et al. 2023

Alz Res Therapy

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Background The over-activation of adenosine A2A receptors (A2AR) is closely implicated in cognitive impairments of Alzheimer's disease (AD). Growing evidence shows that A2AR blockade possesses neuroprotective effects on AD. Spatial navigation impairment is an early manifestation of cognitive deficits in AD. However, whether A2AR blockade can prevent early impairments in spatial cognitive function and the underlying mechanism is still unclear. Methods A transgenic APP/PS1 mouse model of AD amyloidosis was used in this study. Behavioral tests were conducted to observe the protective effects of A2AR blockade on early spatial memory deficits in 4-month old APP/PS1 mice. To investigate the underlying synaptic mechanism of the protective effects of A2AR blockade, we further examined long-term potentiation (LTP) and network excitation/inhibition balance of dentate gyrus (DG) region, which is relevant to unique synaptic functions of immature adult-born granule cells (abGCs). Subsequently, the protective effects of A2AR blockade on dendritic morphology and synaptic plasticity of 6-week-old abGCs was investigated using retrovirus infection and electrophysiological recordings. The molecular mechanisms underlying neuroprotective properties of A2AR blockade on the synaptic plasticity of abGCs were further explored using molecular biology methods. Results APP/PS1 mice displayed DG-dependent spatial memory deficits at an early stage. Additionally, impaired LTP and an imbalance in network excitation/inhibition were observed in the DG region of APP/PS1 mice, indicating synaptic structural and functional abnormalities of abGCs. A2AR was found to be upregulated in the hippocampus of the APP/PS1 mouse model of AD. Treatment with the selective A2AR antagonist SCH58261 for three weeks significantly ameliorated spatial memory deficits in APP/PS1 mice and markedly restored LTP and network excitation/inhibition balance in the DG region. Moreover, SCH58261 treatment restored dendritic morphology complexity and enhanced synaptic plasticity of abGCs in APP/PS1 mice. Furthermore, SCH58261 treatment alleviated the impairment of synaptic plasticity in abGCs. It achieved this by remodeling the subunit composition of NMDA receptors and increasing the proportion of NR2B receptors in abGCs of APP/PS1 mice. Conclusions Blockade of A2AR improves early spatial memory deficits in APP/PS1 mice, possibly by reversing synaptic defects of abGCs. This finding suggests that A2AR blockade could be a potential therapy for AD.

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Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage

Cited by 6 publications

References 74 publications

Advancement in modulation of brain extracellular space and unlocking its potential for intervention of neurological diseases

Advancement in modulation of brain extracellular space and unlocking its potential for intervention of neurological diseases

Contralesional Anodal Transcranial Direct Current Stimulation Promotes Intact Corticospinal Tract Axonal Sprouting and Functional Recovery After Traumatic Brain Injury in Mice

Blockade of adenosine A2A receptors reverses early spatial memory defects in the APP/PS1 mouse model of Alzheimer’s disease by promoting synaptic plasticity of adult-born granule cells

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