NF-kappaB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety.
The ubiquitous transcription factor nuclear factor (NF)-kappaB plays a prominent role in regulation of inflammatory immune responses and in cell survival. Recently, it has been found to be active in neurons, and mice lacking NF-kappaB subunits p50 or p65 show deficits in specific cognitive tasks. Here we demonstrate a strikingly low level of anxiety-like behavior in the p50(-/-) mouse. In an open field, the mutant mice showed significantly less defecation, more rearing, and more time spent in the center compartment relative to wild type control mice. The p50(-/-) mice also spent more time investigating a novel object placed in the open field. On the elevated plus maze, p50(-/-) mice spent more time on the open arms and had increased numbers of open arm entries relative to wild type. In group housing conditions, they did not establish dominant-subordinate hierarchies, whereas wild type control animals did so, in part, by whisker barbering and conspecific allogrooming. In tests of general health, sensorimotor function, and daily activity on a circadian rhythm, p50(-/-) mice were normal. Thus, absence of the p50 subunit of the NF-kappaB transcription factor, which results in altered NF-kappaB transcriptional activity in cells throughout the body and brain, alters neuronal circuitry underlying manifestation of emotional behavior. The p50 subunit appears to play a role in normal expression of certain forms of anxiety.
Section on Functional Neuroanatomy, National Institute of Mental Health, NIH, DHHS, Bldg. 36, Rm. 2D15, Bethesda, MD 20892-4070, USA.
Cheryl A
CA
Kassed
Miles
M
Herkenham
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics; D004328:Drive; D005106:Exploratory Behavior / Q000502:physiology*; D005786:Gene Expression Regulation; D006185:Habituation, Psychophysiologic / Q000502:physiology; D008297:Male; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D016328:NF-kappa B / Q000172:deficiency* / Q000235:genetics; D052002:NF-kappa B p50 Subunit; D011597:Psychomotor Performance; D018709:Statistics, Nonparametric; D013997:Time Factors
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit