Tags

Type your tag names separated by a space and hit enter

Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats.
Neuroscience. 2014 Sep 26; 277:6-13.N

Abstract

Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by cognitive impairment, but effective strategies against AD are currently not available. Interestingly, glucagon-like peptide-1 (GLP-1) used in type 2 diabetes mellitus (T2DM) has shown neuroprotective effects in preclinical studies of AD. Lixisenatide, an effective GLP-1 receptor (GLP-1R) agonist with much longer half life than GLP-1, has been licensed in the EU as a treatment for T2DM. However, the neuroprotective effects of lixisenatide in the brain remain to be clarified. In the present study, we report for the first time the effects of lixisenatide on the amyloid β (Aβ) protein-induced impairments in spatial learning and memory of rats, and investigated its electrophysiological and molecular mechanisms. We found that: (1) bilateral intrahippocampal injection of Aβ25-35 resulted in a significant decline in spatial learning and memory of rats, as well as a suppression of in vivo hippocampal long-term potentiation (LTP); (2) lixisenatide treatment effectively prevented the Aβ25-35-induced impairments; (3) lixisenatide inhibited the Aβ25-35 injection-induced activation of glycogen synthase kinase 3β (GSK3β), with a significant increase in the phosphorylation of ser9 and a significant decrease in the phosphorylation of Y216. These results indicate that lixisenatide, by affecting the PI3K-Akt-GSK3β pathway, can prevent Aβ-related impairments in synaptic plasticity and spatial memory of rats, suggesting that lixisenatide may be a novel and effective treatment for AD.

Authors+Show Affiliations

Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.Division of Biomed and Life Sciences, Faculty of Health and Medicine Lancaster University, Lancaster LA1 4YQ, UK.Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.Second Affiliated Hospital of Shanxi Medical University, Taiyuan 030001, China.Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.Department of Physiology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: jinshunqi2006@yahoo.com.

Pub Type(s)

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

Language

eng

PubMed ID

24583037

Citation

Cai, H-Y, et al. "Lixisenatide Rescues Spatial Memory and Synaptic Plasticity From Amyloid Β Protein-induced Impairments in Rats." Neuroscience, vol. 277, 2014, pp. 6-13.
Cai HY, Hölscher C, Yue XH, et al. Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats. Neuroscience. 2014;277:6-13.
Cai, H. Y., Hölscher, C., Yue, X. H., Zhang, S. X., Wang, X. H., Qiao, F., Yang, W., & Qi, J. S. (2014). Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats. Neuroscience, 277, 6-13. https://doi.org/10.1016/j.neuroscience.2014.02.022
Cai HY, et al. Lixisenatide Rescues Spatial Memory and Synaptic Plasticity From Amyloid Β Protein-induced Impairments in Rats. Neuroscience. 2014 Sep 26;277:6-13. PubMed PMID: 24583037.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats. AU - Cai,H-Y, AU - Hölscher,C, AU - Yue,X-H, AU - Zhang,S-X, AU - Wang,X-H, AU - Qiao,F, AU - Yang,W, AU - Qi,J-S, Y1 - 2014/02/27/ PY - 2014/01/18/received PY - 2014/02/15/revised PY - 2014/02/18/accepted PY - 2014/3/4/entrez PY - 2014/3/4/pubmed PY - 2015/6/9/medline KW - Alzheimer’s disease KW - Morris water maze KW - amyloid β-protein KW - glycogen synthase kinase 3β KW - lixisenatide KW - long-term potentiation SP - 6 EP - 13 JF - Neuroscience JO - Neuroscience VL - 277 N2 - Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by cognitive impairment, but effective strategies against AD are currently not available. Interestingly, glucagon-like peptide-1 (GLP-1) used in type 2 diabetes mellitus (T2DM) has shown neuroprotective effects in preclinical studies of AD. Lixisenatide, an effective GLP-1 receptor (GLP-1R) agonist with much longer half life than GLP-1, has been licensed in the EU as a treatment for T2DM. However, the neuroprotective effects of lixisenatide in the brain remain to be clarified. In the present study, we report for the first time the effects of lixisenatide on the amyloid β (Aβ) protein-induced impairments in spatial learning and memory of rats, and investigated its electrophysiological and molecular mechanisms. We found that: (1) bilateral intrahippocampal injection of Aβ25-35 resulted in a significant decline in spatial learning and memory of rats, as well as a suppression of in vivo hippocampal long-term potentiation (LTP); (2) lixisenatide treatment effectively prevented the Aβ25-35-induced impairments; (3) lixisenatide inhibited the Aβ25-35 injection-induced activation of glycogen synthase kinase 3β (GSK3β), with a significant increase in the phosphorylation of ser9 and a significant decrease in the phosphorylation of Y216. These results indicate that lixisenatide, by affecting the PI3K-Akt-GSK3β pathway, can prevent Aβ-related impairments in synaptic plasticity and spatial memory of rats, suggesting that lixisenatide may be a novel and effective treatment for AD. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/24583037/Lixisenatide_rescues_spatial_memory_and_synaptic_plasticity_from_amyloid_β_protein_induced_impairments_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(14)00133-X DB - PRIME DP - Unbound Medicine ER -