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

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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.

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Data Availability

Data is available on request from the authors.

Abbreviations

AD:

Alzheimer’s disease

Akt:

Protein kinase B

ApoE:

Apolipoprotein E

Aβ:

Amyloid beta

BDNF:

Brain-derived neurotrophic factor

BPA:

Bisphenol A

CA:

Carnosic acid

CREB:

CAMP response element-binding protein

DMEM:

Dulbecco’s Modified Eagle Medium

DMSO:

Dimethyl sulfoxide

ERK:

Extracellular signal-regulated kinase

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

GSK:

Glycogen synthase kinase

HRP:

Horseradish peroxidase

IB:

Immunoblotting

IP assay:

Immunoprecipitation assay

IRS-1:

Insulin response sequence-1

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide

NOR:

Novel object recognition test

OFT:

Open-field test

PSD-95:

Post-synaptic density protein 95

RA:

Retinoic acid

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Funding

This study was supported by the Ministry of Science and Technology (MOST 110–2320-B-039–050-MY3) and the China Medical University (CMU111-MF-77 and CMU112-MF-68).

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Author notes

  1. Shaoi Hsu and Ruhuei Fu contributed equally to this work.

Authors and Affiliations

  1. Department of Nutrition, China Medical University, Taichung, Taiwan

    Shaoi Hsu, Chunhuei Liao, Hsiyun Huang, Yachen Shih, Jingwei Chen, Hanting Wu, Tzuyu Kuo & Chiawen Tsai

  2. Department of Chinese Pharmaceutical Science and Chinese Medicine Resources, China Medical University, Taichung, Taiwan

    Huichi Huang

  3. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

    Ruhuei Fu

  4. Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan

    Ruhuei Fu

  5. Neuroscience and Brain Disease Center, China Medical University, Taichung, Taiwan

    Chiawen Tsai

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  1. Shaoi Hsu
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Contributions

Shaoi Hsu and Ruhuei Fu contributed equally to this work. Data curation and validation were performed by Shaoi Hsu, Huichi Huang, Chunhuei Liao, Hsiyun Huang, Yachen Shih, Jingwei Chen, Hanting Wu, and Tzuyu Kuo. The first draft of the manuscript was written by Shaoi Hsu. Ruhuei Fu performed conceptualization, methodology, resources, and supervision. Chiawen Tsai conceived the project, funding acquisition, project administration, resources, supervision, and writing the final manuscript.

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Correspondence to Chiawen Tsai.

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All animal procedures were evaluated and approved by the Institutional Animal Care and Use Committee of China Medical University (protocol no. CMUIACUC-2021–099-1).

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Highlights

• BPA induced the alternation of insulin signaling and synaptic plasticity in SH-SY5Y cells and mice.

• BPA exposure caused accumulation of p-tau and apo E.

• BPA exposure impairs recognition and memory ability in mice.

• CA and RE improved BPA-induced phosphorylated tau and memory impairment.

• CA and RE prevented BPA-induced adverse effects through Akt pathway.

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Hsu, S., Huang, H., Liao, C. et al. 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). https://doi.org/10.1007/s12035-024-03952-9

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