Presenilin-1 familial Alzheimer's disease mutation alters hippocampal neurogenesis and memory function in CCL2 null mice

Brain Behav Immun. 2015 Oct:49:311-21. doi: 10.1016/j.bbi.2015.06.014. Epub 2015 Jun 22.

Abstract

Aberrations in hippocampal neurogenesis are associated with learning and memory, synaptic plasticity and neurodegeneration in Alzheimer's disease (AD). However, the linkage between them, β-amyloidosis and neuroinflammation is not well understood. To this end, we generated a mouse overexpressing familial AD (FAD) mutant human presenilin-1 (PS1) crossed with a knockout (KO) of the CC-chemokine ligand 2 (CCL2) gene. The PS1/CCL2KO mice developed robust age-dependent deficits in hippocampal neurogenesis associated with impairments in learning and memory, synaptic plasticity and long-term potentiation. Neurogliogenesis gene profiling supported β-amyloid independent pathways for FAD-associated deficits in hippocampal neurogenesis. We conclude that these PS1/CCL2KO mice are suitable for studies linking host genetics, immunity and hippocampal function.

Keywords: Chemokine; Hippocampus; Long-term potentiation; Morris water maze; Neurogliogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology
  • Animals
  • Chemokine CCL2 / genetics*
  • Chemokine CCL2 / metabolism
  • Disease Models, Animal*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Humans
  • Long-Term Potentiation / genetics
  • Maze Learning / physiology
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neurogenesis*
  • Neurons / metabolism
  • Neurons / physiology
  • Presenilin-1 / genetics*
  • Presenilin-1 / metabolism

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • PSEN1 protein, human
  • Presenilin-1