# Electroacupuncture alleviates cognitive impairment in mice with vascular dementia by regulating the cholinergic vasodilation system

**Authors:** Yuanjie Gao, Jianxin Zhao, Jianpeng Chen, Rongming Qi, Yuxuan Yuan, Bohong Liu, Xiaohan Yu, Yaru Liu

PMC · DOI: 10.3389/fnagi.2026.1686345 · Frontiers in Aging Neuroscience · 2026-02-13

## TL;DR

Electroacupuncture improves cognitive function in mice with vascular dementia by enhancing a brain pathway that controls blood vessel dilation.

## Contribution

This study identifies the cholinergic vasodilation system as a novel mechanism through which electroacupuncture alleviates vascular dementia symptoms.

## Key findings

- EA improved cognitive function and dilated cerebral arterioles in VaD mice.
- EA increased acetylcholine and NO levels via upregulation of the ACh/NO pathway.
- The m-1AChR antagonist partially reversed EA's effects, suggesting its key role in the mechanism.

## Abstract

Electroacupuncture (EA) is a potential and reliable treatment for vascular dementia (VaD). This study aims to explore the mechanism of EA in the treatment of VaD based on neurovascular coupling.

The VaD model was established by bilateral common carotid artery occlusion (BCCAO). Mice received EA at Baihui (GV20), Geshu (BL17), and Shenshu (BL23) acupoints for 7 days. Then, behavioral tests, leptomeningeal microvascular observation, immunofluorescence of basal forebrain neurons, and molecular analyses of the ACh/NO pathway were conducted.

EA stimulation alleviated cognitive impairment in VaD mice, dilated leptomeningeal arterioles, enhanced neuronal activity and acetylcholine expression in the basal forebrain, and increased the levels of m-1AChR, α-7-nAChR, eNOS, and NO in the frontal cortex. The m-1AChR antagonist (THP), but not the α-7-nAChR antagonist (MLA), partially reversed these regulatory effects of EA.

EA dilates cerebral arterioles by up-regulating the ACh/NO pathway within cholinergic vasodilation system, thereby alleviating cognitive impairment induced by VaD.

Electroacupuncture dilates cerebral arterioles by up-regulating the ACh/NO pathway within cholinergic vasodilation system, thereby alleviating cognitive impairment induced by vascular dementia. This image was made by figdraw.com. ACh, acetylcholine; eNOS, endothelial nitric oxide synthase; NO, nitric oxide.Diagram illustrating the ACh/NO cholinergic vasodilation pathway showing electroacupuncture applied to a mouse model with bilateral common carotid artery occlusion, cholinergic neuron activation from the basal forebrain, acetylcholine projections, muscarinic receptor binding, increased eNOS and NO production, and arteriole dilation.

Electroacupuncture dilates cerebral arterioles by up-regulating the ACh/NO pathway within cholinergic vasodilation system, thereby alleviating cognitive impairment induced by vascular dementia. This image was made by figdraw.com. ACh, acetylcholine; eNOS, endothelial nitric oxide synthase; NO, nitric oxide.

## Linked entities

- **Proteins:** FGFR3 (fibroblast growth factor receptor 3), Nos1 (nitric oxide synthase 1, neuronal), NOS3 (nitric oxide synthase 3), CHRNA7 (cholinergic receptor nicotinic alpha 7 subunit)
- **Chemicals:** MLA (PubChem CID 494471)
- **Diseases:** vascular dementia (MONDO:0004648)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Fos (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 14281] {aka D12Rfj1, c-fos, cFos}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Smc1a (structural maintenance of chromosomes 1A) [NCBI Gene 24061] {aka 5830426I24Rik, SMC-1A, Sb1.8, Smc1, Smc1alpha, Smc1l1}, nr (nervous) [NCBI Gene 18170], Chrna7 (cholinergic receptor, nicotinic, alpha polypeptide 7) [NCBI Gene 11441] {aka Acra7, alpha7, nAChR7, nAchR}, Cebpz (CCAAT/enhancer binding protein zeta) [NCBI Gene 12607] {aka CBF2, Cbf}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Ints6 (integrator complex subunit 6) [NCBI Gene 18130] {aka 2900075H24Rik, DICE1, Ddx26, HDB, Notch2l}, Nos3 (nitric oxide synthase 3, endothelial cell) [NCBI Gene 18127] {aka 2310065A03Rik, Nos-3, eNOS, ecNOS}, Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}
- **Diseases:** venous congestion (MESH:D006940), blood stasis (MESH:D014647), nausea (MESH:D009325), vomiting (MESH:D014839), Cerebral small vessel disease (MESH:D059345), inflammatory (MESH:D007249), Chronic cerebral hypoperfusion (MESH:D006521), edema (MESH:D004487), thermal injury (MESH:D020886), cerebral ischemia (MESH:D002545), irritability (MESH:D001523), AD (MESH:D000544), dementia (MESH:D003704), infarction (MESH:D007238), neuronal damage (MESH:D009410), memory impairment (MESH:D008569), CCA (MESH:C536211), cognitive impairment (MESH:D003072), dislocation (MESH:D004204), VaD (MESH:D015140), artery occlusion (MESH:D001157), brain lesions (MESH:D001927), bilateral common carotid artery occlusion (MESH:D002340), dizziness (MESH:D004244), ischemic stroke (MESH:D002544), cardiovascular and cerebrovascular diseases (MESH:D002318), agitation (MESH:D011595)
- **Chemicals:** atropine (MESH:D001285), ACh (MESH:D000109), isoflurane (MESH:D007530), arachidonic acid (MESH:D016718), Penicillin sodium (MESH:D010400), water (MESH:D014867), NO (MESH:D009569), ethanol (MESH:D000431), SDS (MESH:D012967), THP (MESH:D014282), acid (MESH:D000143), paraffin (MESH:D010232), THP (MESH:C027260), prostaglandins (MESH:D011453), thromboxane (MESH:D013931), paraformaldehyde (MESH:C003043), nimodipine (MESH:D009553), PVDF (MESH:C024865), citicoline (MESH:D003566), NO (MESH:D009614), BCCAO (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12946052/full.md

## References

64 references — full list in the complete paper: https://tomesphere.com/paper/PMC12946052/full.md

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Source: https://tomesphere.com/paper/PMC12946052