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Sericin Improves Memory Impairment Via Activation of the PKA-CREB-BDNF Signaling Pathway and Suppression of Oxidative Stress in Ovariectomized Mice

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Abstract

Menopause results in estrogen hormone deficiency which causes changes in brain morphology and cognitive impairments. The risk of breast and ovarian cancer increases with estrogen therapy. Thus, finding a substitute treatment option for women in menopause is necessary. In the current study, the impact of chronic sericin treatment (200 mg/kg/day for 6 weeks, gavage) on memory process, oxidative stress markers, synaptic neurotransmission, and acetylcholinesterase (AChE) activity in the hippocampus (HIP) of ovariectomized (OVX) mice was examined and compared to the effects of 17β-estradiol (Es; 20 µg/kg, s.c.). The results demonstrated that sericin and Es administration improved spatial and recognition memory of the OVX animals in the both Lashley III maze and novel object recognition tests. Moreover, sericin-treated OVX mice showed decreased ROS levels, increased endogenous antioxidant defense capacity, and decreased AChE activity in the HIP. Additionally, sericin and Es therapy up-regulated pre-and-post-synaptic protein markers and increased BDNF, CREB, and protein kinase A (PKA) protein expressions in the HIP of OVX mice. Overall, the activation of the PKA-CREB-BDNF signaling pathway by sericin can provide protection against OVX-induced cognitive dysfunction, making it a potential alternative for managing cognitive deficits in postmenopausal women.

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Data Availability

The data that support the findings of this study can be obtained from the corresponding author upon reasonable request.

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Funding

This work was supported in part by a grant (no: 63894) awarded to Dr. Javad Mahmoudi from Tabriz University of Medical Sciences (Tabriz, Iran).

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Authors and Affiliations

  1. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, 5166614756, Iran

    Fereshteh Farajdokht, Saeed Sadigh-Eteghad, Seyedmahdi Vatandoust, Soroush Morsali, Pedram Ghaderi Shadbad & Javad Mahmoudi

  2. Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Leila Hosseini

  3. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Soroush Morsali & Hamidreza Feizi

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  1. Fereshteh Farajdokht
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Contributions

JM and FF conceived and designed the study. FF, SMV, and JM performed the experiments and collected the data. SSE and PGS analyzed the data. The first draft of the manuscript was written by SM, HF, and LH. All authors commented on previous versions of the manuscript, and reviewed and approved the final version of the manuscript.

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Correspondence to Javad Mahmoudi.

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Farajdokht, F., Sadigh-Eteghad, S., Vatandoust, S. et al. Sericin Improves Memory Impairment Via Activation of the PKA-CREB-BDNF Signaling Pathway and Suppression of Oxidative Stress in Ovariectomized Mice. Neurochem Res 49, 1093–1104 (2024). https://doi.org/10.1007/s11064-023-04094-5

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