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Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats.
Neurol Sci. 2014 May; 35(5):741-51.NS

Abstract

Recent evidence indicates that severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer's disease pathology. It has been reported that naringenin (NAR), derived from citrus aurantium, exhibits antioxidant potential and protects the brain against neurodegeneration. The current study was designed to further investigate the protective effect of the NAR on neurodegeneration in a rat model of AD induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ), and to determine whether this neuroprotective effect was associated with brain insulin signaling. Rats were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle and then supplemented with NAR (25, 50 mg, 100 mg/kg, respectively) for 3 weeks. The ICV-STZ injected rats did not have elevated blood glucose levels. 21 days following ICV-STZ injection, rats treated with NAR had better learning and memory performance in the Morris water maze test compared with rats treated with saline. We demonstrated that NAR increased the mRNA expression of INS and INSR in cerebral cortex and hippocampus. In addition, NAR reversed ICV-STZ induced Tau hyper-phosphorylation in both hippocampus and cerebral cortex through downregulation of glycogen synthase kinase-3β (GSK-3β) activity, a key kinase in the insulin signaling. Brain levels of Abeta, which were elevated in ICV-STZ rats, were significantly reduced in NAR-treated rats via upregulation of insulin degrading enzyme. These effects were mediated by increased insulin and insulin receptors expression in the brain, suggesting that insulin sensitizer agents might have therapeutic efficacy in early AD.

Authors+Show Affiliations

Department of Physiology, Research Center of Neuroscience, Chongqing Medical University, Chongqing, 400016, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24337945

Citation

Yang, Wenqing, et al. "Effect of Naringenin On Brain Insulin Signaling and Cognitive Functions in ICV-STZ Induced Dementia Model of Rats." Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, vol. 35, no. 5, 2014, pp. 741-51.
Yang W, Ma J, Liu Z, et al. Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats. Neurol Sci. 2014;35(5):741-51.
Yang, W., Ma, J., Liu, Z., Lu, Y., Hu, B., & Yu, H. (2014). Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats. Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 35(5), 741-51. https://doi.org/10.1007/s10072-013-1594-3
Yang W, et al. Effect of Naringenin On Brain Insulin Signaling and Cognitive Functions in ICV-STZ Induced Dementia Model of Rats. Neurol Sci. 2014;35(5):741-51. PubMed PMID: 24337945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats. AU - Yang,Wenqing, AU - Ma,Jing, AU - Liu,Zheng, AU - Lu,Yongliang, AU - Hu,Bin, AU - Yu,Huarong, Y1 - 2013/12/12/ PY - 2013/06/27/received PY - 2013/11/28/accepted PY - 2013/12/17/entrez PY - 2013/12/18/pubmed PY - 2015/1/28/medline SP - 741 EP - 51 JF - Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology JO - Neurol. Sci. VL - 35 IS - 5 N2 - Recent evidence indicates that severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer's disease pathology. It has been reported that naringenin (NAR), derived from citrus aurantium, exhibits antioxidant potential and protects the brain against neurodegeneration. The current study was designed to further investigate the protective effect of the NAR on neurodegeneration in a rat model of AD induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ), and to determine whether this neuroprotective effect was associated with brain insulin signaling. Rats were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle and then supplemented with NAR (25, 50 mg, 100 mg/kg, respectively) for 3 weeks. The ICV-STZ injected rats did not have elevated blood glucose levels. 21 days following ICV-STZ injection, rats treated with NAR had better learning and memory performance in the Morris water maze test compared with rats treated with saline. We demonstrated that NAR increased the mRNA expression of INS and INSR in cerebral cortex and hippocampus. In addition, NAR reversed ICV-STZ induced Tau hyper-phosphorylation in both hippocampus and cerebral cortex through downregulation of glycogen synthase kinase-3β (GSK-3β) activity, a key kinase in the insulin signaling. Brain levels of Abeta, which were elevated in ICV-STZ rats, were significantly reduced in NAR-treated rats via upregulation of insulin degrading enzyme. These effects were mediated by increased insulin and insulin receptors expression in the brain, suggesting that insulin sensitizer agents might have therapeutic efficacy in early AD. SN - 1590-3478 UR - https://www.unboundmedicine.com/medline/citation/24337945/Effect_of_naringenin_on_brain_insulin_signaling_and_cognitive_functions_in_ICV_STZ_induced_dementia_model_of_rats_ L2 - https://dx.doi.org/10.1007/s10072-013-1594-3 DB - PRIME DP - Unbound Medicine ER -