In the world of Alzheimer’s disease, the protein aquaporin-4 (AQP4) is like a traffic cop directing the flow of fluid in the brain. However, in the case of Alzheimer’s, this traffic cop gets lost and can’t do its job properly. Enter moxibustion, like a GPS for AQP4! Moxibustion is a traditional Chinese therapy that involves burning dried plant materials near specific points on the body to stimulate healing. Researchers wanted to see if moxibustion could help get AQP4 back on track in Alzheimer’s mouse models. They used spatial transcriptomics to analyze how moxibustion affected AQP4 polarization at the blood-brain barrier. The results showed that moxibustion improved the abnormal polarization of AQP4, particularly in the hypothalamus. Additionally, other genes related to AQP4 showed similar improvements with moxibustion treatment. To shed light on the mechanism behind these improvements, researchers investigated mitochondrial energy supply and found that moxibustion increased the expression of enzymes involved in energy metabolism. This suggests that targeting mitochondrial energy supply could be an important way to improve cognitive impairment in Alzheimer’s. So, hop on board the research train and explore more about this exciting study!

Aquaporin-4 (AQP4) is highly polarized to perivascular astrocytic endfeet. Loss of AQP4 polarization is associated with many diseases. In Alzheimer’s disease (AD), AQP4 loses its normal location and thus reduces the clearance of amyloid-β plaques and tau protein. Clinical and experimental studies showed that moxibustion can improve the learning and memory abilities of AD. To explore whether moxibustion can affect the polarization of AQP4 around the blood-brain barrier (BBB), we used spatial transcriptomics (ST) to analyze the expression and polarization of Aqp4 in wild-type mice, APP/PS1 mice, and APP/PS1 mice intervened by moxibustion. The results showed that moxibustion improved the loss of abnormal polarization of AQP4 in APP/PS1 mice, especially in the hypothalamic BBB. Besides, the other 31 genes with Aqp4 as the core have similar depolarization in APP/PS1 mice, most of which are also membrane proteins. The majority of them have been reversed by moxibustion. At the same time, we employed the cerebrospinal fluid circulation gene set, which was found to be at a higher level in the group of APP/PS1 mice with moxibustion treatment. Finally, to further explore its mechanism, we analyzed the mitochondrial respiratory chain complex enzymes closely related to energy metabolism and found that moxibustion can significantly increase the expression of mitochondrial respiratory chain enzymes such as Cox6a2 in the hypothalamus, which could provide energy for mRNA transport. Our research shows that increasing the polarization of hypothalamic Aqp4 through mitochondrial energy supply may be an important target for moxibustion to improve cognitive impairment in APP/PS1 mice.

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