Background
Electroacupuncture (EA) is a complementary and alternative therapy which has shown protective effects on vascular cognitive impairment (VCI). However, the underlying mechanisms are not entirely understood.
Conclusion
Inhibition of miR-219a ameliorates VCI by regulating NMDAR-mediated synaptic plasticity in animal models of cerebral ischemia.
Methods
Rat models of VCI were established with cerebral ischemia using occlusion of the middle cerebral artery or bilateral common carotid artery. The brain structure and function imaging were measured through animal MRI. miRNA expression was detected by chip and qPCR. Synaptic functional plasticity was detected using electrophysiological techniques.
Results
This study demonstrated the enhancement of Regional Homogeneity (ReHo) activity of blood oxygen level-dependent (BOLD) signal in the entorhinal cortical (EC) and hippocampus (HIP) in response to EA treatment. miR-219a was selected and confirmed to be elevated in HIP and EC in VCI but decreased after EA. N-methyl-D-aspartic acid receptor1 (NMDAR1) was identified as the target gene of miR-219a. miR-219a regulated NMDAR-mediated autaptic currents, spontaneous excitatory postsynaptic currents (sEPSC), and long-term potentiation (LTP) of the EC-HIP CA1 circuit influencing synaptic plasticity. EA was able to inhibit miR-219a, enhancing synaptic plasticity of the EC-HIP CA1 circuit and increasing expression of NMDAR1 while promoting the phosphorylation of downstream calcium/calmodulin-dependent protein kinase II (CaMKII), improving overall learning and memory in VCI rat models.