PMID- 22072675 OWN - NLM STAT- MEDLINE DCOM- 20120104 LR - 20220331 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 31 IP - 45 DP - 2011 Nov 9 TI - CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. PG - 16241-50 LID - 10.1523/JNEUROSCI.3667-11.2011 [doi] AB - The protective/neurotoxic role of fractalkine (CX3CL1) and its receptor CX3C chemokine receptor 1 (CX3CR1) signaling in neurodegenerative disease is an intricate and highly debated research topic and it is becoming even more complicated as new studies reveal discordant results. It appears that the CX3CL1/CX3CR1 axis plays a direct role in neurodegeneration and/or neuroprotection depending on the CNS insult. However, all the above studies focused on the role of CX3CL1/CX3CR1 signaling in pathological conditions, ignoring the relevance of CX3CL1/CX3CR1 signaling under physiological conditions. No approach to date has been taken to decipher the significance of defects in CX3CL1/CX3CR1 signaling in physiological condition. In the present study we used CX3CR1(-)/(-), CX3CR1(+)/(-), and wild-type mice to investigate the physiological role of CX3CR1 receptor in cognition and synaptic plasticity. Our results demonstrate for the first time that mice lacking the CX3CR1 receptor show contextual fear conditioning and Morris water maze deficits. CX3CR1 deficiency also affects motor learning. Importantly, mice lacking the receptor have a significant impairment in long-term potentiation (LTP). Infusion with IL-1beta receptor antagonist significantly reversed the deficit in cognitive function and impairment in LTP. Our results reveal that under physiological conditions, disruption in CX3CL1 signaling will lead to impairment in cognitive function and synaptic plasticity via increased action of IL-1beta. FAU - Rogers, Justin T AU - Rogers JT AD - Department of Molecular Pharmacology and Physiology, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, Florida 33612, USA. FAU - Morganti, Josh M AU - Morganti JM FAU - Bachstetter, Adam D AU - Bachstetter AD FAU - Hudson, Charles E AU - Hudson CE FAU - Peters, Melinda M AU - Peters MM FAU - Grimmig, Bethany A AU - Grimmig BA FAU - Weeber, Edwin J AU - Weeber EJ FAU - Bickford, Paula C AU - Bickford PC FAU - Gemma, Carmelina AU - Gemma C LA - eng GR - P01 AG004418/AG/NIA NIH HHS/United States GR - P01 AG004418-27/AG/NIA NIH HHS/United States GR - P01 AG030128/AG/NIA NIH HHS/United States GR - AG-04418/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Aif1 protein, mouse) RN - 0 (Calcium-Binding Proteins) RN - 0 (Cytokines) RN - 0 (Interleukin 1 Receptor Antagonist Protein) RN - 0 (Microfilament Proteins) RN - 0 (Receptors, Interleukin-8A) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Analysis of Variance MH - Animals MH - Behavior, Animal/drug effects/physiology MH - Biophysics MH - Bromodeoxyuridine/metabolism MH - Calcium-Binding Proteins/genetics/metabolism MH - Cerebellum/metabolism MH - Cognition Disorders/genetics/*pathology MH - Conditioning, Psychological/physiology MH - Cytokines/metabolism MH - Disease Models, Animal MH - Electric Stimulation MH - Enzyme-Linked Immunosorbent Assay/methods MH - Excitatory Postsynaptic Potentials/drug effects/genetics MH - Exploratory Behavior/physiology MH - Fear/physiology MH - Gene Expression Regulation/genetics MH - Hippocampus/*pathology/*physiopathology MH - In Vitro Techniques MH - Interleukin 1 Receptor Antagonist Protein/pharmacology MH - Long-Term Potentiation/*genetics/physiology MH - Male MH - Maze Learning/physiology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Microfilament Proteins/genetics/metabolism MH - Microglia/pathology MH - Motor Activity/genetics MH - Neurogenesis/genetics MH - Patch-Clamp Techniques MH - Receptors, Interleukin-8A/*deficiency MH - Rotarod Performance Test PMC - PMC3236509 MID - NIHMS340599 EDAT- 2011/11/11 06:00 MHDA- 2012/01/05 06:00 PMCR- 2012/05/09 CRDT- 2011/11/11 06:00 PHST- 2011/11/11 06:00 [entrez] PHST- 2011/11/11 06:00 [pubmed] PHST- 2012/01/05 06:00 [medline] PHST- 2012/05/09 00:00 [pmc-release] AID - 31/45/16241 [pii] AID - 3733753 [pii] AID - 10.1523/JNEUROSCI.3667-11.2011 [doi] PST - ppublish SO - J Neurosci. 2011 Nov 9;31(45):16241-50. doi: 10.1523/JNEUROSCI.3667-11.2011.