Inhibition of Microglial Activation Protects Hippocampal Neurogenesis and Improves Cognitive Deficits in a Transgenic Mouse Model for Alzheimer's Disease

Background: Activated microglia with macrophage-like functions invade and surround beta-amyloid (A beta) plaques in Alzheimer's disease (AD), possibly contributing to the turnover of A beta, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis. Objectives/Methods: To determine the role of microglia on neurogenesis in brains with A beta 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 A beta and A beta-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 A beta-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 A beta pathology. Copyright (C) 2012 S. Karger AG, Basel

Lindvall, OlleLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurogenes och Cellterapi,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Neurogenesis and cell therapy,Lund University Research Groups(Swepub:lu)neur-oli (author)
Tesco, Giuseppina (author)
Ekdahl Clementson, ChristineLund University,Lunds universitet,Epilepsicentrum,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk neurofysiologi,Institutionen för kliniska vetenskaper, Lund,Epilepsy Center,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Neurophysiology,Department of Clinical Sciences, Lund(Swepub:lu)neur-cek (author)
Nitsch, Roger M. (author)
Neurologi, LundSektion IV (creator_code:org_t)

By the author/editor: Biscaro, Barbara; Lindvall, Olle; Tesco, Giuseppin ...; Ekdahl Clementso ...; Nitsch, Roger M.

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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