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Alzheimer's disease (AD) is one of the most serious public health concerns facing the world. Its characteristic feature is neuroinflammation due to microglial activation. Electroacupuncture is one of the therapies employed to improve the condition of patients with AD, although its mechanism of action is still to be determined. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor that is involved in regulating neuroinflammation in AD. In this study, we applied senescence-accelerated mouse-prone 8 mice as the AD animal model, used the Morris water maze, and applied hematoxylin and eosin staining, immunofluorescence double staining, and Western blotting, to explore the effects and potential mechanisms of action of electroacupuncture. In summary, this study suggested that electroacupuncture treatment could improve the learning and memory abilities (p < 0.05) and protect neurons. These effects result from acupuncture could upregulate TREM2 expression in the hippocampus (p < 0.01), which was essential for the anti-inflammatory effects in the AD animal model. However, further studies are needed to conclusively demonstrate the mechanism of action of electroacupuncture in AD. [ABSTRACT FROM AUTHOR]

• New designed poly (β amino esters) (PBAE) nano-platform can achieve mRNA delivery to brain and spinal cord efficiently. • Stable mRNA secondary structures were engineered by AI and contributed to higher protein expressions. • 3′UTR of mRNA was engineered to achieve neuron selective delivery with less side effects. Brain-derived neurotrophic factor (BDNF) has a long history in the treatment neurodegenerative of diseases. However, this therapy has limitations in exogenous protein safety, including side effects like neuropathic pain and seizures. Moreover, there are currently no positive clinical trial results using BDNF-based gene therapy. Given this, new methods of delivering BDNF are urgently needed. Here, we report an engineering BDNF mRNA-based therapy in a murine model of Alzheimer's disease (AD). Two poly (β amino esters) polymers (PBAE) were synthesized, which achieved mRNA delivery to brain and spinal cord efficiently following catheter ventricle pumping. To confer stability and RNase resistance, the secondary structure of the mRNA was engineering using AI algorithms. Further mRNA modification was done on 3′ untranslated region (3′UTR), which was added with neuron-specific miRNA targeting sequence to avoid BDNF protein expression in neuron. This allowed reduced neuronal overexcitation and seizures. And BDNF protein was sustained released from astrocytes to maintain surrounding neural function. The engineering mRNA was delivered into the brain ventricle and translated into astrocytes to significantly improve the memory of AD mice. Given the mRNA modifications presented here, it would de-target delivery to specific cell types and has therapeutic potential for the treatment of neurological diseases. [ABSTRACT FROM AUTHOR]