title: PPARγ activation prevents impairments in spatial memory and neurogenesis following transient illness.
abstract: The detrimental effects of illness on cognition are familiar to virtually everyone. Some effects resolve quickly while others may linger after the illness resolves. We found that a transient immune response stimulated by lipopolysaccharide (LPS) compromised hippocampal neurogenesis and impaired hippocampus-dependent spatial memory. The immune event caused an ∼50% reduction in the number of neurons generated during the illness and the onset of the memory impairment was delayed and coincided with the time when neurons generated during the illness would have become functional within the hippocampus. Broad spectrum non-steroidal anti-inflammatory drugs attenuated these effects but selective Cox-2 inhibition was ineffective while PPARγ activation was surprisingly effective at protecting both neurogenesis and memory from the effects of LPS-produced transient illness. These data may highlight novel mechanisms behind chronic inflammatory and neuroinflammatory episodes that are known to compromise hippocampus-dependent forms of learning and memory.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, McKnight Brain Institute and Neuroscience Department, University of Florida, Gainesville, FL 32611, USA. Electronic address: bormerod@bme.ufl.edu.
authors.forename: Brandi K
authors.initials: BK
authors.lastname: Ormerod
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Hanft
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, McKnight Brain Institute and Neuroscience Department, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Asokan
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Haditsch
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Star W
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: tpalmer@stanford.edu.
authors.forename: Theo D
authors.initials: TD
authors.lastname: Palmer
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002452:Cell Count; D003627:Data Interpretation, Statistical; D005260:Female; D006624:Hippocampus / Q000502:physiology; D055809:Illness Behavior / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D055495:Neurogenesis / Q000502:physiology*; D047495:PPAR gamma / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000963:Antimetabolites; D008070:Lipopolysaccharides; D047495:PPAR gamma; D001973:Bromodeoxyuridine