PMID- 23031643
OWN - NLM
STAT- MEDLINE
DCOM- 20130419
LR  - 20211021
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 9
DP  - 2012 Oct 3
TI  - Expression of myeloid differentiation factor 88 in neurons is not requisite for 
      the induction of sickness behavior by interleukin-1beta.
PG  - 229
LID - 10.1186/1742-2094-9-229 [doi]
AB  - BACKGROUND: Animals respond to inflammation by suppressing normal high-energy 
      activities, including feeding and locomotion, in favor of diverting resources to 
      the immune response. The cytokine interleukin-1 beta (IL-1beta) inhibits normal 
      feeding and locomotor activity (LMA) via its actions in the central nervous 
      system (CNS). Behavioral changes in response to IL-1beta are mediated by myeloid 
      differentiation factor 88 (MyD88) in non-hematopoietic cells. It is unknown 
      whether IL-1beta acts directly on neurons or requires transduction by non-neuronal 
      cells. METHODS: The Nestin-cre mouse was crossed with MyD88lox mice to delete 
      MyD88 from neurons and glia in the CNS (MyD88DeltaCNS). These mice were compared to 
      total body MyD88KO and wild type (WT) mice. Mice had cannulae stereotactically 
      placed in the lateral ventricle and telemetry transponders implanted into the 
      peritoneum. Mice were treated with either intracerebroventricular (i.c.v.) IL-1beta 
      (10 ng) or vehicle. Food intake, body weight and LMA were continuously monitored 
      for 24 h after treatment. I.c.v. tumor necrosis factor (TNF), a MyD88-independent 
      cytokine, was used to control for normal immune development. Peripheral 
      inflammation was modeled using intraperitoneal lipopolysaccharide (LPS). Groups 
      were compared using two-way ANOVA with Bonferroni post-test. Efficacy of 
      recombination was evaluated using tdTomato reporter mice crossed with the 
      Nestin-cre mouse. MyD88 deletion was confirmed by Western blot. RESULTS: I.c.v. 
      IL-1beta treatment caused a significant reduction in feeding, body weight and LMA in 
      WT mice. MyD88KO mice were protected from these changes in response to i.c.v. 
      IL-1beta despite having intact behavioral responses to TNF. Cre-mediated 
      recombination was observed in neurons and astrocytes, but not microglia or 
      endothelial cells. In contrast to MyD88KO mice, the behavioral responses of 
      MyD88DeltaCNS mice to i.c.v. IL-1beta or intraperitoneal (i.p.) LPS were 
      indistinguishable from those of WT mice. CONCLUSION: Sickness behavior is 
      mediated by MyD88 and is dependent on the activity of cytokines within the brain. 
      Our results demonstrate that MyD88 is not required in neurons or astrocytes to 
      induce this behavioral response to IL-1beta or LPS. This suggests that a non-Nestin 
      expressing cell population responds to IL-1beta in the CNS and transduces the signal 
      to neurons controlling feeding and activity.
FAU - Braun, Theodore P
AU  - Braun TP
AD  - Pape Family Pediatric Research Institute, Oregon Health and Science University, 
      Portland, OR 97239, USA.
FAU - Grossberg, Aaron J
AU  - Grossberg AJ
FAU - Veleva-Rotse, Biliana O
AU  - Veleva-Rotse BO
FAU - Maxson, Julia E
AU  - Maxson JE
FAU - Szumowski, Marek
AU  - Szumowski M
FAU - Barnes, Anthony P
AU  - Barnes AP
FAU - Marks, Daniel L
AU  - Marks DL
LA  - eng
GR  - 200948/CAPMC/CIHR/Canada
GR  - DK 70333/DK/NIDDK NIH HHS/United States
GR  - DK 084711/DK/NIDDK NIH HHS/United States
GR  - DK 084646/DK/NIDDK NIH HHS/United States
GR  - F30 DK084646/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121003
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Intermediate Filament Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nes protein, mouse)
RN  - 0 (Nestin)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Brain/cytology
MH  - Cells, Cultured
MH  - Embryo, Mammalian
MH  - Gene Expression Regulation/*drug effects/genetics
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Illness Behavior/*drug effects
MH  - Injections, Intraventricular
MH  - Interleukin-1beta/*administration & dosage
MH  - Intermediate Filament Proteins/genetics/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Motor Activity/drug effects
MH  - Myeloid Differentiation Factor 88/deficiency/genetics/*metabolism
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Nestin
MH  - Neurons/*drug effects/metabolism
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/pharmacology
PMC - PMC3488557
EDAT- 2012/10/04 06:00
MHDA- 2013/04/23 06:00
PMCR- 2012/10/03
CRDT- 2012/10/04 06:00
PHST- 2012/04/23 00:00 [received]
PHST- 2012/09/25 00:00 [accepted]
PHST- 2012/10/04 06:00 [entrez]
PHST- 2012/10/04 06:00 [pubmed]
PHST- 2013/04/23 06:00 [medline]
PHST- 2012/10/03 00:00 [pmc-release]
AID - 1742-2094-9-229 [pii]
AID - 10.1186/1742-2094-9-229 [doi]
PST - epublish
SO  - J Neuroinflammation. 2012 Oct 3;9:229. doi: 10.1186/1742-2094-9-229.