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Effects of CREB1 gene silencing on cognitive dysfunction by mediating PKA-CREB signaling pathway in mice with vascular dementia.
Mol Med. 2018 05 03; 24(1):18.MM

Abstract

BACKGROUND

As a form of dementia primarily affecting the elderly, vascular dementia (VD) is characterized by changes in the supply of blood to the brain, resulting in cognitive impairment. The aim of the present study was to explore the effects involved with cyclic adenosine monophosphate (cAMP) response element-binding (CREB)1 gene silencing on cognitive dysfunction through meditation of the protein kinase A (PKA)-CREB signaling pathway in mice with VD.

METHODS

Both the Morris water maze test and the step down test were applied to assess the cognitive function of the mice with VD. Immunohistochemical and TUNEL staining techniques were employed to evaluate the positive expression rates of the protein CREB1 and Cleaved Caspase-3, as well as neuronal apoptosis among hippocampal tissues in a respective manner. Flow cytometry was applied to determine the proliferation index and apoptosis rate of the hippocampal cells among each group. Reverse transcription quantitative polymerase chain reaction and Western blot analysis methods were applied to detect the expressions of cAMP, PKA and CREB in hippocampal cells.

RESULTS

Compared with the normal group, all the other groups exhibited impaired cognitive function, reduced cell numbers in the CAI area, positive expressions of CREB1 as well as positive optical density (OD) values. Furthermore, increased Cleaved Caspase-3 positive expression, OD value, proliferation index, apoptosis rate of hippocampal cells and neurons, were observed in the other groups when compared with the normal group, as well as lower expressions of cAMP, PKA and CREB1 and p-CREB1 (the shCREB1-1, H89 and shCREB1-1 + H89 groups < the VD group).

CONCLUSION

The key findings of the present study demonstrated that CREB1 gene silencing results in aggravated VD that occurs as a result of inhibiting the PKA-CREB signaling pathway, thus exasperating cognitive dysfunction.

Authors+Show Affiliations

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. wdm8610@jsnu.edu.cn. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. wdm8610@jsnu.edu.cn.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. lu-jun75@163.com. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. lu-jun75@163.com.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. ylzheng@jsnu.edu.cn. College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China. ylzheng@jsnu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30134805

Citation

Han, Xin-Rui, et al. "Effects of CREB1 Gene Silencing On Cognitive Dysfunction By Mediating PKA-CREB Signaling Pathway in Mice With Vascular Dementia." Molecular Medicine (Cambridge, Mass.), vol. 24, no. 1, 2018, p. 18.
Han XR, Wen X, Wang YJ, et al. Effects of CREB1 gene silencing on cognitive dysfunction by mediating PKA-CREB signaling pathway in mice with vascular dementia. Mol Med. 2018;24(1):18.
Han, X. R., Wen, X., Wang, Y. J., Wang, S., Shen, M., Zhang, Z. F., Fan, S. H., Shan, Q., Wang, L., Li, M. Q., Hu, B., Sun, C. H., Wu, D. M., Lu, J., & Zheng, Y. L. (2018). Effects of CREB1 gene silencing on cognitive dysfunction by mediating PKA-CREB signaling pathway in mice with vascular dementia. Molecular Medicine (Cambridge, Mass.), 24(1), 18. https://doi.org/10.1186/s10020-018-0020-y
Han XR, et al. Effects of CREB1 Gene Silencing On Cognitive Dysfunction By Mediating PKA-CREB Signaling Pathway in Mice With Vascular Dementia. Mol Med. 2018 05 3;24(1):18. PubMed PMID: 30134805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of CREB1 gene silencing on cognitive dysfunction by mediating PKA-CREB signaling pathway in mice with vascular dementia. AU - Han,Xin-Rui, AU - Wen,Xin, AU - Wang,Yong-Jian, AU - Wang,Shan, AU - Shen,Min, AU - Zhang,Zi-Feng, AU - Fan,Shao-Hua, AU - Shan,Qun, AU - Wang,Liang, AU - Li,Meng-Qiu, AU - Hu,Bin, AU - Sun,Chun-Hui, AU - Wu,Dong-Mei, AU - Lu,Jun, AU - Zheng,Yuan-Lin, Y1 - 2018/05/03/ PY - 2018/02/24/received PY - 2018/04/20/accepted PY - 2018/8/24/entrez PY - 2018/8/24/pubmed PY - 2019/1/19/medline KW - CREB KW - CREB1 KW - Cognitive dysfunction KW - PKA KW - Signaling pathway KW - Vascular dementia SP - 18 EP - 18 JF - Molecular medicine (Cambridge, Mass.) JO - Mol Med VL - 24 IS - 1 N2 - BACKGROUND: As a form of dementia primarily affecting the elderly, vascular dementia (VD) is characterized by changes in the supply of blood to the brain, resulting in cognitive impairment. The aim of the present study was to explore the effects involved with cyclic adenosine monophosphate (cAMP) response element-binding (CREB)1 gene silencing on cognitive dysfunction through meditation of the protein kinase A (PKA)-CREB signaling pathway in mice with VD. METHODS: Both the Morris water maze test and the step down test were applied to assess the cognitive function of the mice with VD. Immunohistochemical and TUNEL staining techniques were employed to evaluate the positive expression rates of the protein CREB1 and Cleaved Caspase-3, as well as neuronal apoptosis among hippocampal tissues in a respective manner. Flow cytometry was applied to determine the proliferation index and apoptosis rate of the hippocampal cells among each group. Reverse transcription quantitative polymerase chain reaction and Western blot analysis methods were applied to detect the expressions of cAMP, PKA and CREB in hippocampal cells. RESULTS: Compared with the normal group, all the other groups exhibited impaired cognitive function, reduced cell numbers in the CAI area, positive expressions of CREB1 as well as positive optical density (OD) values. Furthermore, increased Cleaved Caspase-3 positive expression, OD value, proliferation index, apoptosis rate of hippocampal cells and neurons, were observed in the other groups when compared with the normal group, as well as lower expressions of cAMP, PKA and CREB1 and p-CREB1 (the shCREB1-1, H89 and shCREB1-1 + H89 groups < the VD group). CONCLUSION: The key findings of the present study demonstrated that CREB1 gene silencing results in aggravated VD that occurs as a result of inhibiting the PKA-CREB signaling pathway, thus exasperating cognitive dysfunction. SN - 1528-3658 UR - https://www.unboundmedicine.com/medline/citation/30134805/Effects_of_CREB1_gene_silencing_on_cognitive_dysfunction_by_mediating_PKA_CREB_signaling_pathway_in_mice_with_vascular_dementia_ L2 - https://doi.org/10.1186/s10020-018-0020-y DB - PRIME DP - Unbound Medicine ER -