title: Inhibition of microglial activation protects hippocampal neurogenesis and improves cognitive deficits in a transgenic mouse model for Alzheimer's disease.
abstract: BACKGROUND
  Activated microglia with macrophage-like functions invade and surround β-amyloid (Aβ) plaques in Alzheimer's disease (AD), possibly contributing to the turnover of Aβ, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis.
  
  
  OBJECTIVE
  To determine the role of microglia on neurogenesis in brains with Aβ pathology, we inhibited microglial activation with the tetracycline derivative minocycline in doubly transgenic mice expressing mutant human amyloid precursor protein (APP) and mutant human presenilin-1 (PS1).
  
  
  RESULTS
  Minocycline increased the survival of new dentate granule cells in APP/PS1 mice indicated by more BrdU+/NeuN+ cells as compared to vehicle-treated transgenic littermates, accompanied by improved behavioral performance in a hippocampus-dependent learning task. Both brain levels of Aβ and Aβ-related morphological deficits in the new neurons labeled with GFP-expressing retrovirus were unaffected in minocycline-treated mice.
  
  
  CONCLUSIONS
  These results suggest a role for microglia in Aβ-related functional deficits and in suppressing the survival of new neurons, and show that modulation of microglial function with minocycline can protect hippocampal neurogenesis in the presence of Aβ pathology.
authors.affiliation: Division of Psychiatry Research, University of Zurich, Zurich, Switzerland. b.biscaro@gmail.com
authors.forename: Barbara
authors.initials: B
authors.lastname: Biscaro
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Tesco
authors.forename: Christine T
authors.initials: CT
authors.lastname: Ekdahl
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology* / Q000517:prevention & control; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000503:physiopathology* / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D009154:Mutation / Q000235:genetics; D055495:Neurogenesis / Q000502:physiology*; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D000893:Anti-Inflammatory Agents; D053764:Presenilin-1; D008911:Minocycline