Autophagosomes accumulation is associated with β-amyloid deposits and secondary damage in the thalamus after focal cortical infarction in hypertensive rats

J Neurochem. 2012 Feb;120(4):564-73. doi: 10.1111/j.1471-4159.2011.07496.x. Epub 2011 Oct 20.

Abstract

Focal cerebral cortical infarction after distal middle cerebral artery occlusion causes β-amyloid deposition and secondary neuronal degeneration in the ipsilateral ventroposterior nucleus of the thalamus. Several studies suggest that autophagy is an active pathway for β-amyloid peptide generation. This study aimed to investigate the role of autophagy in thalamic β-amyloid deposition and neuronal degeneration after cerebral cortical infarction in hypertensive rats. At 7 and 14days after middle cerebral artery occlusion, neuronal death and β-amyloid deposits were evident in the ipsilateral ventroposterior nucleus, and the activity of β-site amyloid precursor protein (APP)-cleaving enzyme 1, required for β-amyloid peptide generation, was elevated in the thalamus. In correlation, both the number of cells showing punctate microtubule-associated protein 1A light chain 3 fluorescence and levels of light chain 3-II protein, an autophagosome marker, were markedly increased. Notably, most of the cells that over-expressed β-site APP-cleaving enzyme 1 displayed punctate light chain 3 staining. Furthermore, the inhibition of autophagy with 3-methyladenine significantly reduced the thalamic neuronal damage, β-amyloid deposits, and β-site APP-cleaving enzyme 1 activity. These results suggest that autophagosomes accumulate within thalamic cells after cerebral cortical infarction, which is associated with thalamic β-amyloid deposition and secondary neuronal degeneration via elevation of β-site APP-cleaving enzyme 1 level.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / biosynthesis
  • Amyloid Precursor Protein Secretases / physiology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / physiology
  • Animals
  • Aspartic Acid Endopeptidases / biosynthesis
  • Aspartic Acid Endopeptidases / physiology
  • Autophagy / physiology*
  • Cerebral Infarction / enzymology
  • Cerebral Infarction / metabolism
  • Cerebral Infarction / pathology*
  • Hypertension / enzymology
  • Hypertension / metabolism
  • Hypertension / pathology*
  • Male
  • Nerve Degeneration / enzymology
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Phagosomes / enzymology
  • Phagosomes / metabolism
  • Phagosomes / pathology*
  • Plaque, Amyloid / enzymology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Thalamus / enzymology
  • Thalamus / metabolism
  • Thalamus / pathology*

Substances

  • Amyloid beta-Peptides
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, rat