Intracerebroventricular Infusion of Angiotensin-(1-7) Ameliorates Cognitive Impairment and Memory Dysfunction in a Mouse Model of Alzheimer's Disease

J Alzheimers Dis. 2016 Apr 23;53(1):127-33. doi: 10.3233/JAD-150642.

Abstract

This work was performed to test our hypothesis that angiotensin-(1-7) can ameliorate cognitive impairment and cerebrovascular reactivity in 5XFAD mice, a useful model of Alzheimer's disease. 5XFAD mice received intracerebroventricular infusion of (1) vehicle, (2) angiotensin-(1-7), or (3) angiotensin-(1-7)+A779, a specific Mas receptor antagonist, for 4 weeks. Angiotensin-(1-7), through Mas receptor, significantly ameliorated cognitive impairment in 5XFAD mice. As estimated by acetazolamide-induced increase in cerebral blood flow, angiotensin-(1-7), through Mas receptor, enhanced cerebrovascular reactivity in 5XFAD mice. In conclusion, angiotensin-(1-7)/Mas receptor axis improves cognitive function and cerebrovascular function in a mouse model of Alzheimer's disease.

Keywords: Acetazolamide; Mas receptor; angiotensin-(1–7); cognitive function; vascular reactivity; water maze test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / pharmacology
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / metabolism
  • Angiotensin I / administration & dosage*
  • Animals
  • Avoidance Learning / drug effects
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Cerebrovascular Circulation / drug effects
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology*
  • Disease Models, Animal
  • Drug Delivery Systems
  • Infusions, Intraventricular
  • Maze Learning / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology*
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / administration & dosage*
  • Reaction Time / drug effects
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Carbonic Anhydrase Inhibitors
  • Peptide Fragments
  • tau Proteins
  • Angiotensin I
  • angiotensin I (1-7)
  • Acetazolamide