Apolipoprotein E deficiency increased microglial activation/CCR3 expression and hippocampal damage in kainic acid exposed mice

Rui Sheng Duan, Zhiguo Chen, Ying Chun Dou, Hernan Concha Quezada, Inger Nennesmo, Abdu Adem, Bengt Winblad, Jie Zhu

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Apolipoprotein E (apoE) down-regulates microglial activation and the secretion of inflammatory molecules in an isoform specific fashion (E2 > E3 > E4); the E4 isoform is over-represented in Alzheimer cases while E2 is under-represented. To better define the role of apoE in neurodegeneration, we contrasted apoE knockout (n = 38) and wild-type mice (n = 41) with respect to seizure activity, mortality, locomotion, hippocampal microglial activation/chemokine receptor expression, and damage to the hippocampus after nasal administration of kainic acid (KA) (water as controls). Mice lacking apoE demonstrated more hunching and less rearing, more damage to neurons in the CA3 region (mean histopathologic score: 3.7 vs. 1.6, p < 0.05), greater microglial activation confirmed by high levels of CD11b and CD86 expression in hippocampus (CD11b p < 0.01, CD86 p < 0.05), and a greater percentage of activated microglia expressing CC chemokine receptors 3 (CCR3) (p < 0.05). Taken together, these findings imply that apoE modulates hippocampal damage induced by KA and found early in the sequence of human Alzheimer's brain changes, by modulating microglial activation.

Original languageBritish English
Pages (from-to)373-380
Number of pages8
JournalExperimental Neurology
Volume202
Issue number2
DOIs
StatePublished - Dec 2006

Keywords

  • apoE
  • CCR3
  • Kainic acid
  • Microglia
  • Neurodegeneration

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