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Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorylation, and microglial activation in a streptozotocin-induced Alzheimer's rat model.
Sci Rep. 2017 04 06; 7:45971.SR

Abstract

Recent evidence reveals that aberrant brain insulin signaling plays an important role in the pathology of Alzheimer's disease (AD). Intranasal insulin administration has been reported to improve memory and attention in healthy participants and in AD patients. However, the underlying molecular mechanisms are poorly understood. Here, we treated intracerebroventricular streptozotocin-injected (ICV-STZ) rats, a commonly used animal model of sporadic AD, with daily intranasal delivery of insulin (2 U/day) for 6 consecutive weeks and then studied their cognitive function with the Morris water maze test and biochemical changes via Western blotting. We observed cognitive deficits, tau hyperphosphorylation, and neuroinflammation in the brains of ICV-STZ rats. Intranasal insulin treatment for 6 weeks significantly improved cognitive function, attenuated the level of tau hyperphosphorylation, ameliorated microglial activation, and enhanced neurogenesis in ICV-STZ rats. Additionally, our results indicate that intranasal delivery of insulin probably attenuates tau hyperphosphorylation through the down-regulation of ERK1/2 and CaMKII in the brains of ICV-STZ rats. Our findings demonstrate a beneficial effect of intranasal insulin and provide the mechanistic basis for treating AD patients with intranasal insulin.

Authors+Show Affiliations

Department of Neurology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.Department of Neurology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.Department of Neurology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.Department of Neurology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.Department of Neurology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.Department of Neurology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.Department of Neurology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.Department of Neurology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.

Pub Type(s)

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

Language

eng

PubMed ID

28382978

Citation

Guo, Zhangyu, et al. "Long-term Treatment With Intranasal Insulin Ameliorates Cognitive Impairment, Tau Hyperphosphorylation, and Microglial Activation in a Streptozotocin-induced Alzheimer's Rat Model." Scientific Reports, vol. 7, 2017, p. 45971.
Guo Z, Chen Y, Mao YF, et al. Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorylation, and microglial activation in a streptozotocin-induced Alzheimer's rat model. Sci Rep. 2017;7:45971.
Guo, Z., Chen, Y., Mao, Y. F., Zheng, T., Jiang, Y., Yan, Y., Yin, X., & Zhang, B. (2017). Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorylation, and microglial activation in a streptozotocin-induced Alzheimer's rat model. Scientific Reports, 7, 45971. https://doi.org/10.1038/srep45971
Guo Z, et al. Long-term Treatment With Intranasal Insulin Ameliorates Cognitive Impairment, Tau Hyperphosphorylation, and Microglial Activation in a Streptozotocin-induced Alzheimer's Rat Model. Sci Rep. 2017 04 6;7:45971. PubMed PMID: 28382978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorylation, and microglial activation in a streptozotocin-induced Alzheimer's rat model. AU - Guo,Zhangyu, AU - Chen,Yanxing, AU - Mao,Yan-Fang, AU - Zheng,Tingting, AU - Jiang,Yasi, AU - Yan,Yaping, AU - Yin,Xinzhen, AU - Zhang,Baorong, Y1 - 2017/04/06/ PY - 2016/11/18/received PY - 2017/03/07/accepted PY - 2017/4/7/entrez PY - 2017/4/7/pubmed PY - 2018/11/18/medline SP - 45971 EP - 45971 JF - Scientific reports JO - Sci Rep VL - 7 N2 - Recent evidence reveals that aberrant brain insulin signaling plays an important role in the pathology of Alzheimer's disease (AD). Intranasal insulin administration has been reported to improve memory and attention in healthy participants and in AD patients. However, the underlying molecular mechanisms are poorly understood. Here, we treated intracerebroventricular streptozotocin-injected (ICV-STZ) rats, a commonly used animal model of sporadic AD, with daily intranasal delivery of insulin (2 U/day) for 6 consecutive weeks and then studied their cognitive function with the Morris water maze test and biochemical changes via Western blotting. We observed cognitive deficits, tau hyperphosphorylation, and neuroinflammation in the brains of ICV-STZ rats. Intranasal insulin treatment for 6 weeks significantly improved cognitive function, attenuated the level of tau hyperphosphorylation, ameliorated microglial activation, and enhanced neurogenesis in ICV-STZ rats. Additionally, our results indicate that intranasal delivery of insulin probably attenuates tau hyperphosphorylation through the down-regulation of ERK1/2 and CaMKII in the brains of ICV-STZ rats. Our findings demonstrate a beneficial effect of intranasal insulin and provide the mechanistic basis for treating AD patients with intranasal insulin. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/28382978/Long_term_treatment_with_intranasal_insulin_ameliorates_cognitive_impairment_tau_hyperphosphorylation_and_microglial_activation_in_a_streptozotocin_induced_Alzheimer's_rat_model_ L2 - http://dx.doi.org/10.1038/srep45971 DB - PRIME DP - Unbound Medicine ER -