title: Analysis of cognition, motor performance and anxiety in young and aged tumor necrosis factor alpha receptor 1 and 2 deficient mice.
abstract: TNF-α plays important functional roles in the central nervous system during normal physiological circumstances via intricate signaling mechanisms between its receptors, TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Although the roles of TNFR1 and TNFR2 in the diseased brain have received considerable attention, their functions on behavior and cognition in a non-inflammatory physiological aged environment are still unknown. In the present study we investigated the functional roles of TNFR1 and TNFR2 in learning and memory, motor performance and anxiety-like behavior via several behavioral and cognitive assessments in young and aged mice, deficient of either TNFR1 or TNFR2. Results from this study show that deletion of TNFR2 impairs novel object recognition, spatial memory recognition, contextual fear conditioning, motor performance and can increase anxiety-like behavior in young adult mice. Concerning the functions of TNFR1 and TNFR2 functioning in an aged environment, age caused memory impairment in spatial memory recognition independent of genotype. However, both young and aged mice deficient of TNFR2 performed poorly in the contextual fear conditioning test. These mice displayed decreased anxiety-like behavior, whereas mice deficient of TNFR1 were insusceptible to the effect of aging on anxiety-like behavior. This study provides novel knowledge on TNFR1 and TNFR2 functioning in behavior and cognition in young and aged mice in a non-inflammatory physiological environment.
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Petrus J W
authors.initials: PJ
authors.lastname: Naude
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Dobos
authors.forename: Dennis
authors.initials: D
authors.lastname: van der Meer
authors.forename: Cornelis
authors.initials: C
authors.lastname: Mulder
authors.forename: Kim G D
authors.initials: KG
authors.lastname: Pawironadi
authors.forename: Johan A
authors.initials: JA
authors.lastname: den Boer
authors.forename: Eddy A
authors.initials: EA
authors.lastname: van der Zee
authors.forename: Paul G M
authors.initials: PG
authors.lastname: Luiten
authors.forename: Ulrich L M
authors.initials: UL
authors.lastname: Eisel
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II
keywords: Aging; Anxiety; Behavior; Contextual fear conditioning; Novel object recognition; Spatial recognition memory