Elevated CSF and plasma microparticles in a rat model of streptozotocin-induced cognitive impairment

Behav Brain Res. 2013 Nov 1:256:503-11. doi: 10.1016/j.bbr.2013.09.019. Epub 2013 Sep 12.

Abstract

Alzheimer's disease (AD), can be described as a vascular disorder, is characterized by endothelial and platelet activation. One feature of activated cells is loss of lipid asymmetry, and membrane blebbing which cause microparticle (MP) formation. MPs increased under many pathological states and little information is available relating to their changes in AD. The purpose of this work was to characterize the time course of the endothelial-derived microparticles (EMPs) and platelet-derived microparticles (PMPs) alteration after intracerebroventricular (ICV) injection of streptozotocin (STZ). Rats were injected bilaterally with ICV-STZ/Saline, cerebrospinal fluid (CSF) and plasma EMPs (Annexin V(+) CD61(-)CD144(+)) and PMPs (Annexin V(+) CD61(+)CD144(-)) were analyzed with flow cytometry at 2 h, 4 h, 24 h, 4 days, 7 days, 14 days and 21 days after ICV-STZ/Saline administration. Cognitive impairment, malondialdehyde (MDA) level of hippocampus, plasma serotonin, and serum S100B were also assessed. We showed the elevation of CSF and plasma level of EMPs and PMPs, which may represent a proinflammatory and prothrombotic status. These alterations were simultaneous with the hippocampal MDA rise, plasma serotonin increment, and S100B decrement, 7 days after ICV-STZ administration and precede the onset of cognitive impairment. Understanding the profile of MP changes in CSF or plasma as biomarkers from tissues undergoing activation or damage, may be helpful in prediction or early diagnosis of AD.

Keywords: AD; ALT; AST; Alzheimer; Alzheimer disease; CBC; CSF; Dementia; EMPs; FSC; ICV-STZ; MDA; MP; MWM; Membrane-derived vesicles; PFP; PMPs; PPP; RBC; SSC; WBC; alanine aminotransferase; aspartate aminotransferase; cerebrospinal fluid; complete blood count; endothelial-derived microparticles; forward scatter; intracerebroventricular-streptozotocin; malondialdehyde; microparticle; morris water maze test; platelet-derived microparticles; platelet-free plasma; platelet-poor plasma; red blood cell; side scatter; white blood cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5 / metabolism
  • Antigens, CD / metabolism
  • Behavior, Animal
  • Cadherins / metabolism
  • Cell-Derived Microparticles / metabolism*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / metabolism*
  • Disease Models, Animal
  • Hippocampus / metabolism*
  • Integrin beta3 / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Maze Learning / physiology
  • Motor Activity / physiology
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism
  • Streptozocin

Substances

  • Annexin A5
  • Antigens, CD
  • Cadherins
  • Integrin beta3
  • cadherin 5
  • Serotonin
  • Malondialdehyde
  • Streptozocin