Induction of Phosphorylated Tau Accumulation and Memory Impairment by Bisphenol A and the Protective Effects of Carnosic Acid in In Vitro and In Vivo

Shaoi Hsu; Huichi Huang; Chunhuei Liao; Hsiyun Huang; Yachen Shih; Jingwei Chen; Hanting Wu; Tzuyu Kuo; Ruhuei Fu; Chiawen Tsai

doi:10.1007/s12035-024-03952-9

Induction of Phosphorylated Tau Accumulation and Memory Impairment by Bisphenol A and the Protective Effects of Carnosic Acid in In Vitro and In Vivo

Mol Neurobiol. 2024 Jan 27. doi: 10.1007/s12035-024-03952-9. Online ahead of print.

Authors

Shaoi Hsu^#¹, Huichi Huang², Chunhuei Liao¹, Hsiyun Huang¹, Yachen Shih¹, Jingwei Chen¹, Hanting Wu¹, Tzuyu Kuo¹, Ruhuei Fu^#^{3

4}, Chiawen Tsai^{5

6}

Affiliations

¹ Department of Nutrition, China Medical University, Taichung, Taiwan.
² Department of Chinese Pharmaceutical Science and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
³ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁴ Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan.
⁵ Department of Nutrition, China Medical University, Taichung, Taiwan. cwtsai@mail.cmu.edu.tw.
⁶ Neuroscience and Brain Disease Center, China Medical University, Taichung, Taiwan. cwtsai@mail.cmu.edu.tw.

^# Contributed equally.

PMID: 38280110
DOI: 10.1007/s12035-024-03952-9

Abstract

Bisphenol A (BPA) is a component of polycarbonate plastics that has been implicated in memory impairment. The present study investigated the effect of carnosic acid (CA) on memory deficit induced by BPA and the role of Akt in this mechanism. First, SH-SY5Y cells were treated with 20 nM BPA and 1 μM CA for 12 h. The results showed that treatment of CA with BPA improved the alternation of IRS-1/Akt/GSK-3β as well as the induction of ApoE and ^Ser396p-tau. Moreover, treatment of CA with BPA restored the signaling involved in long-term potentiation (LTP) effect, leading to induction of synaptic-related proteins, such as PSD-95, synapsin1a, and pro-BDNF. Wortmannin treatment alleviated the reversal by CA. Then, C57BL/6 J male mice were orally administered with CA to test the memory function in BPA treatment. The results showed that CA and RE can improve BPA-induced impairment of motor, recognition, and spatial memory by using open-field test (OFT), novel objective recognition test (NOR), and Y-maze test, respectively. Moreover, CA and RE improved the phosphorylation of tau and the reduction of PSD-95, synapsin1a, and pro-BDNF proteins induced by BPA. Therefore, the results indicated that CA decreased the phosphorylated tau and memory impairment induced by BPA through Akt pathway.

Keywords: Bisphenol A; C57BL/6 mice; Carnosic acid; Memory; SH-SY5Y cells; Synaptic plasticity.

Abstract

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