title: Intranasal administration of Exendin-4 antagonizes Aβ31-35-induced disruption of circadian rhythm and impairment of learning and memory.
abstract: BACKGROUND
  The deposition of β-amyloid protein (Aβ) is one of the pathological characteristics of Alzheimer's disease (AD) and can disrupt circadian rhythm and impair learning and memory. Exendin-4, a therapeutic drug for type II diabetes mellitus (T2DM), exerts neuroprotective effects from the toxicity of Aβ. However, it is not clear whether Exendin-4 protects against Aβ-induced disruption of circadian rhythm. The neuroprotective effects of Exendin-4 have been studied using injection of Exendin-4 into the lateral ventricle and abdomen. However, these procedures are not suitable for clinical application.
  
  
  METHODS
  First, male C57BL/6 mice received triple distilled water or Exendin-4 (0.1 nmol, 0.5 nmol) by intranasal administration. Exendin-4 levels were measured in the hippocampal samples using an ELISA Kit. Then, the study examined whether intranasal or hippocampal administration of Exendin-4 antagonized Aβ-induced disruption of circadian rhythm as well as impairment of learning and memory using the wheel-running activity assay and the Morris water maze test.
  
  
  RESULTS
  The study showed that intranasally administered Exendin-4 passed through the blood-brain barrier. Aβ31-35 given by intrahippocampal injection disrupted circadian rhythm and impaired learning and memory in C57BL/6 mice, and Exendin-4 given by nasal cavity or hippocampal administration ameliorated Aβ31-35-induced circadian rhythm disturbance of locomotor activity and impairment of learning and memory.
  
  
  CONCLUSIONS
  These findings provide pivotal experimental support for further study of the neuroprotective effects and clinical application of Exendin-4.
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, 030001, China. 163.wangxh@163.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D000077270:Exenatide; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010455:Peptides; D014688:Venoms; C113042:amyloid beta-protein (31-35); D000077270:Exenatide
keywords: Ameliorate; Circadian rhythm; Exendin-4; Intranasal administration; Learning and memory