Fulopova Barbora, Bennett William, Canty Alison J
The University of Queensland, The Queensland Brain Institute, St. Lucia, Queensland, Australia.
University of Tasmania, Wicking Dementia Research and Education Centre, Hobart, Tasmania, Australia.
Neurophotonics. 2025 Jan;12(Suppl 1):S14613. doi: 10.1117/1.NPh.12.S1.S14613. Epub 2025 May 28.
Growing evidence highlights the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) in diseases causing dementias such as Alzheimer's disease (AD). However, individual responses to rTMS are variable, and its underlying neural mechanisms are not fully understood.
As synaptic dysfunction is one of the key mechanisms associated with cognitive deficits in dementia, we investigated the effect of rTMS on cortical synapses using an APP/PS1 amyloidosis mouse model of AD crossed with fluorescent reporters linked to the Thy-1 promoter.
Using two-photon imaging, we characterized the plasticity of excitatory (TB) and (EPB) axonal boutons at 48-h intervals for 8 days on either side of a single session of rTMS.
We found both types of axonal boutons preserved the overall number of their synaptic outputs in wild type (WT) and APP/PS1 groups, pre- and post-stimulation. Both synapse types also showed a significantly reduced dynamic fraction in APP/PS1 compared with WT axons pre-stimulation. Following stimulation, the TB, but not EPB, dynamic fraction increased in both WT and APP/PS1 groups.
This suggests possible mechanisms of rTMS action that are cell type-specific and, together with previous findings of improved functional performance, present a potential clinical avenue for rTMS in the management of AD.
越来越多的证据凸显了重复经颅磁刺激（rTMS）在治疗诸如阿尔茨海默病（AD）等导致痴呆症的疾病方面的潜力。然而，个体对rTMS的反应存在差异，其潜在的神经机制尚未完全明确。
由于突触功能障碍是痴呆症认知缺陷相关的关键机制之一，我们使用与Thy-1启动子相连的荧光报告基因的AD APP/PS1淀粉样变性小鼠模型，研究rTMS对皮质突触的影响。
我们采用双光子成像技术，在单次rTMS治疗前后的8天内，每隔48小时对兴奋性（TB）和（EPB）轴突终扣的可塑性进行表征。
我们发现，在野生型（WT）和APP/PS1组中，刺激前后两种类型的轴突终扣都保持了其突触输出的总数。与刺激前的WT轴突相比，APP/PS1组中两种突触类型的动态分数也显著降低。刺激后，WT组和APP/PS1组中的TB动态分数增加，但EPB动态分数未增加。
这表明rTMS作用的可能机制具有细胞类型特异性，并且与先前功能改善的研究结果一起，为rTMS在AD治疗中提供了一条潜在的临床途径。
