title: Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration.
abstract: BACKGROUND
  In Alzheimer's disease, stroke and brain injuries, activated microglia can release proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines may change astrocyte and neurotrophin functions, which influences neuronal survival and induces apoptosis. However, the interaction between neuroinflammation and neurotrophin functions in different brain conditions is unknown. The present study hypothesized that acute and subacute elevated IL-1β differentially modulates glial and neurotrophin functions, which are related to their role in neuroprotection and neurodegeneration.
  
  
  METHODS
  Rats were i.c.v. injected with saline or IL-1β for 1 or 8 days and tested in a radial maze. mRNA and protein expressions of glial cell markers, neurotrophins, neurotrophin receptors, β-amyloid precursor protein (APP) and the concentrations of pro- and anti-inflammatory cytokines were measured in the hippocampus.
  
  
  RESULTS
  When compared to controls, memory deficits were found 4 days after IL-1 administrations, however the deficits were attenuated by IL-1 receptor antagonist (RA). Subacute IL-1 administrations increased expressions of APP, microglial active marker CD11b, and p75 neurotrophin receptor, and the concentration of tumor necrosis factor (TNF)-α and IL-1β, but decreased expressions of astrocyte active marker glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and TrK B. By contrast, up-regulations of NGF, BDNF and TrK B expressions were found after acute IL-1 administration, which are associated with the increase in both glial marker expressions and IL-10 concentrations. However, TrK A was down-regulated by acute and up-regulated by subacute IL-1 administrations. Subacute IL-1-induced changes in the glial activities, cytokine concentrations and expressions of BDNF and p75 were reversed by IL-1RA treatment.
  
  
  CONCLUSIONS
  These results indicate that acute and subacute IL-1 administrations induce different changes toward neuroprotection after acute IL-1 administrations but neurodegeneration after subacute ones.
authors: Research Institute of Marine Drug and Nutrition, Guangdong Ocean University, Zhanjiang, Guangdong, China. cai.song@dal.ca
authors: Cai
authors: C
authors: Song
authors: Ye
authors: Y
authors: Zhang
authors: Yilong
authors: Y
authors: Dong
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009410:Nerve Degeneration / Q000473:pathology*; D009414:Nerve Growth Factors / Q000378:metabolism*; D009420:Nervous System / Q000187:drug effects / Q000276:immunology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D051381:Rats; D020318:Rats, Long-Evans; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D039481:CD11b Antigen; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB
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