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Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats.
J Alzheimers Dis. 2015; 47(1):61-71.JA

Abstract

Here, we investigated the effect of escitalopram pretreatment on protein kinase A (PKA)-induced tau hyperphosphorylation and spatial memory deficits in rats using western blot and behavioral tests, respectively. We demonstrated that escitalopram effectively ameliorated tau hyperphosphorylation and the spatial memory deficits induced by PKA activation. We measured the total and activity-dependent Ser9-phosphorylated levels of glycogen synthase kinase (GSK)-3β in hippocampal extracts. No significant change in the total level of GSK-3β was observed between the different groups. However, compared with forskolin injection alone, pretreatment with escitalopram increased the level of Ser9-phosphorylated GSK-3β. We also demonstrated that escitalopram increased Akt phosphorylation at Ser473 (the active form of Akt). Furthermore, we identified other important kinases and phosphatases, such as protein phosphatase 2A, extracellular signal-regulated kinases 1 and 2, and MAP kinase kinase-1/2, that have previously been reported to play a crucial role in tau phosphorylation; however, we did not detect any significant change in the activation of these kinases or phosphatases in our study. We unexpectedly demonstrated that forskolin caused anxiety-like behavior in rats, and pretreatment with escitalopram did not significantly ameliorate the anxiety-like behavior induced by forskolin. These data provide the first evidence that escitalopram ameliorates forskolin-induced tau hyperphosphorylation and spatial memory impairment in rats; these effects do not occur via the anti-anxiety activity of escitalopram but may involve the Akt/GSK-3β signaling pathway.

Authors+Show Affiliations

Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China. Graduate School of Chinese Academy of Sciences, Beijing, China.Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.

Pub Type(s)

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

Language

eng

PubMed ID

26402755

Citation

Ren, Qing-Guo, et al. "Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced By Protein Kinase a Activation in Sprague Dawley Rats." Journal of Alzheimer's Disease : JAD, vol. 47, no. 1, 2015, pp. 61-71.
Ren QG, Wang YJ, Gong WG, et al. Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats. J Alzheimers Dis. 2015;47(1):61-71.
Ren, Q. G., Wang, Y. J., Gong, W. G., Xu, L., & Zhang, Z. J. (2015). Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats. Journal of Alzheimer's Disease : JAD, 47(1), 61-71. https://doi.org/10.3233/JAD-143012
Ren QG, et al. Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced By Protein Kinase a Activation in Sprague Dawley Rats. J Alzheimers Dis. 2015;47(1):61-71. PubMed PMID: 26402755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats. AU - Ren,Qing-Guo, AU - Wang,Yan-Juan, AU - Gong,Wei-Gang, AU - Xu,Lin, AU - Zhang,Zhi-Jun, PY - 2015/9/25/entrez PY - 2015/9/25/pubmed PY - 2016/6/29/medline KW - Alzheimer’s disease KW - PKA KW - escitalopram KW - tau SP - 61 EP - 71 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 47 IS - 1 N2 - Here, we investigated the effect of escitalopram pretreatment on protein kinase A (PKA)-induced tau hyperphosphorylation and spatial memory deficits in rats using western blot and behavioral tests, respectively. We demonstrated that escitalopram effectively ameliorated tau hyperphosphorylation and the spatial memory deficits induced by PKA activation. We measured the total and activity-dependent Ser9-phosphorylated levels of glycogen synthase kinase (GSK)-3β in hippocampal extracts. No significant change in the total level of GSK-3β was observed between the different groups. However, compared with forskolin injection alone, pretreatment with escitalopram increased the level of Ser9-phosphorylated GSK-3β. We also demonstrated that escitalopram increased Akt phosphorylation at Ser473 (the active form of Akt). Furthermore, we identified other important kinases and phosphatases, such as protein phosphatase 2A, extracellular signal-regulated kinases 1 and 2, and MAP kinase kinase-1/2, that have previously been reported to play a crucial role in tau phosphorylation; however, we did not detect any significant change in the activation of these kinases or phosphatases in our study. We unexpectedly demonstrated that forskolin caused anxiety-like behavior in rats, and pretreatment with escitalopram did not significantly ameliorate the anxiety-like behavior induced by forskolin. These data provide the first evidence that escitalopram ameliorates forskolin-induced tau hyperphosphorylation and spatial memory impairment in rats; these effects do not occur via the anti-anxiety activity of escitalopram but may involve the Akt/GSK-3β signaling pathway. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/26402755/Escitalopram_Ameliorates_Tau_Hyperphosphorylation_and_Spatial_Memory_Deficits_Induced_by_Protein_Kinase_A_Activation_in_Sprague_Dawley_Rats_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-143012 DB - PRIME DP - Unbound Medicine ER -