Brain-derived neurotrophic factor mRNA downregulation produced by social isolation is blocked by intrahippocampal interleukin-1 receptor antagonist.
Manipulations that increase the expression of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in the hippocampus (e.g. peripheral administration of lipopolysaccharide, i.c.v. glycoprotein 120, social isolation) as well as the intrahippocampal injection of IL-1beta following a learning experience, dramatically impair the memory of that experience if the formation of the memory requires the hippocampus. Here we employed social isolation to further study this phenomenon, as well as its relation to brain-derived neurotrophic factor (BDNF). BDNF was studied because of its well-documented role in the formation of hippocampally based memory. A 6 h period of social isolation immediately after contextual fear conditioning impaired memory for context fear measured 48 h later, and decreased BDNF mRNA in the dentate gyrus and the CA3 region of the hippocampus assessed immediately after the isolation. Moreover, an intrahippocampal injection of the IL-1 receptor antagonist prior to the isolation period prevented both the BDNF downregulation and the memory impairments produced by the isolation. These data suggest that hippocampal-dependent memory impairments induced by elevated levels of brain IL-1beta may occur via an IL-1beta-induced downregulation in hippocampal BDNF.
Department of Psychology and Center for Neuroscience, Campus Box 345, University of Colorado at Boulder, Boulder, CO 80309, USA. rbarr@psych.colorado.edu
R M
RM
Barrientos
D B
DB
Sprunger
S
S
Campeau
E A
EA
Higgins
L R
LR
Watkins
J W
JW
Rudy
S F
SF
Maier
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012795:Sialoglycoproteins / Q000494:pharmacology*; D012934:Social Isolation / Q000523:psychology*; D013315:Stress, Psychological / Q000235:genetics / Q000276:immunology
D019208:Brain-Derived Neurotrophic Factor; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins