Inflammation is detrimental for neurogenesis in adult brain.
New hippocampal neurons are continuously generated in the adult brain. Here, we demonstrate that lipopolysaccharide-induced inflammation, which gives rise to microglia activation in the area where the new neurons are born, strongly impairs basal hippocampal neurogenesis in rats. The increased neurogenesis triggered by a brain insult is also attenuated if it is associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. The impaired neurogenesis in inflammation is restored by systemic administration of minocycline, which inhibits microglia activation. Our data raise the possibility that suppression of hippocampal neurogenesis by activated microglia contributes to cognitive dysfunction in aging, dementia, epilepsy, and other conditions leading to brain inflammation.
Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, Biomedical Center A-11, Lund, Sweden.
Christine T
CT
Ekdahl
Jan-Hendrik
JH
Claasen
Sara
S
Bonde
Zaal
Z
Kokaia
Olle
O
Lindvall
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D000963:Antimetabolites; D008070:Lipopolysaccharides; D008911:Minocycline; D001973:Bromodeoxyuridine