Spatial transcriptomics shows moxibustion promotes hippocampus astrocyte and neuron interaction.

AIMS:Alzheimer's disease (AD) is a common and irreversible neurodegenerative disease accompanied by extensive synaptic loss. Previous studies found that moxibustion had good therapeutic effects on AD. We here investigated whether moxibustion could alleviate the cognitive impairment of AD by promoting the "astrocyte-neuron" interaction and enhancing synaptic plasticity. MATERIALS AND METHODS:Moxibustion treatment was administrated to Baihui (GV20) and Yongquan (KI1) in APP/PS1 mice. We first evaluated the behavior of APP/PS1 mice with Morris water maze test, and observed the synaptic structure before and after moxibustion intervention. Then, the transcriptome characteristics (TC) and "astrocyte-neuron" interaction were evaluated by spatial transcriptomics (ST). CD38 and its ligand Pecam1, one of the energy shuttle pathways between neurons and astrocytes, were also be detected. KEY FINDINGS:The results supported that moxibustion increased learning and memory ability and synaptic structure. ST showed that the TC were more similar between the moxibustion and control groups. Moxibustion enhanced the number of ligand - receptor pairs between astrocytes and neurons. And the score of interaction intensity and the proportion of interaction were also increased. Meanwhile, the energy of astrocytes and neurons was significantly altered. Additionally, moxibustion could significantly improve the function of CD38 and its ligand Pecam1 which were previously reported having the function of transporting mitochondria from astrocytes to neurons, and then providing energy for neurons. SIGNIFICANCE:Our study provides new evidences for the use of moxibustion to increase the "astrocyte - neuron" interaction thus to enhance synaptic plasticity of APP/PS1 mice.