Fat mass and obesity-associated protein regulates RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion

Wang，Yanqing1; Wu，Zimei2,4; He，Yuyang5; Zeng，Xiaoying6; Gu，Zijuan7; Zhou，Xianxi1; Si，Wenwen3; Chen，Dongfeng1

2024-06-01

10.1016/j.npep.2024.102428

Neuropeptides   影响因子和分区

0143-4179

1532-2785

RNA methylation can epigenetically regulate learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of Vascular dementia (VD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus in models of VD. Through prediction and dual-luciferase reporters validation studies, we observed that miRNA-711 was upregulated after VD and could bind to the 3′-untranslated region of FTO mRNA and regulate its expression in vitro. Methylated RNA immunoprecipitation (MeRIP)-qPCR assay and functional study confirmed that Syn1 was an important target gene of FTO. This suggests that FTO is an important regulator of Syn1. FTO upregulation by inhibition of miR-711 in the hippocampus relieves synaptic association protein and synapse deterioration in vivo, whereas FTO downregulation by miR-711 agomir in the hippocampus leads to aggravate the synapse deterioration. FTO upregulation by inhibition of miR-711 relieves cognitive impairment of rats VD model, whereas FTO downregulation by miR-711 deteriorate cognitive impairment. Our findings suggest that FTO is a regulator of a mechanism underlying RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion.

Cognitive impairment FTO Mir-711 Synaptic loss Vascular dementia

SCI

英语

其他

NEUROSCIENCE & BEHAVIOR

2-s2.0-85189431032

Scopus

1.Department of Anatomy,School of Basic Medical Sciences,Guangzhou University of Chinese Medicine,Guangzhou,China
2.Department of Orthopedic Surgery,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,China
3.School of Integrated Chinese and Western Medicine,Anhui University of Chinese Medicine,Hefei,China
4.School of Medicine,Southern University of Science and Technology,Shenzhen,China
5.The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine,Shenzhen Traditional Chinese Medicine Hospital,Shenzhen,China
6.Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine,Guangzhou University of Chinese Medicine,Shenzhen,China
7.Shenzhen BaoAn District Traditional Chinese Medicine Hospital,Guangzhou University of Chinese Medicine,Shenzhen,China

Wang，Yanqing,Wu，Zimei,He，Yuyang,et al. Fat mass and obesity-associated protein regulates RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion[J]. Neuropeptides,2024,105.

Wang，Yanqing.,Wu，Zimei.,He，Yuyang.,Zeng，Xiaoying.,Gu，Zijuan.,...&Chen，Dongfeng.(2024).Fat mass and obesity-associated protein regulates RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion.Neuropeptides,105.

Wang，Yanqing,et al."Fat mass and obesity-associated protein regulates RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion".Neuropeptides 105(2024).