Interleukin (IL)-1 and IL-6 regulation of neural progenitor cell proliferation with hippocampal injury: differential regulatory pathways in the subgranular zone (SGZ) of the adolescent and mature mouse brain.
Current data suggests an association between elevations in interleukin 1 (IL-1)α, IL-1β, and IL-6 and the proliferation of neural progenitor cells (NPCs) following brain injury. A limited amount of work implicates changes in these pro-inflammatory responses with diminished NPC proliferation observed as a function of aging. In the current study, adolescent (21day-old) and 1year-old CD-1 male mice were injected with trimethyltin (TMT, 2.3mg/kg, i.p.) to produce acute apoptosis of hippocampal dentate granule cells. In this model, fewer 5-bromo-2'-deoxyuridine (BrdU)+ NPC were observed in both naive and injured adult hippocampus as compared to the corresponding number seen in adolescent mice. At 48h post-TMT, a similar level of neuronal death was observed across ages, yet activated ameboid microglia were observed in the adolescent and hypertrophic process-bearing microglia in the adult. IL-1α mRNA levels were elevated in the adolescent hippocampus; IL-6 mRNA levels were elevated in the adult. In subgranular zone (SGZ) isolated by laser-capture microdissection, IL-1β was detected but not elevated by TMT, IL-1a was elevated at both ages, while IL-6 was elevated only in the adult. Naïve NPCs isolated from the hippocampus expressed transcripts for IL-1R1, IL-6Rα, and gp130 with significantly higher levels of IL-6Rα mRNA in the adult. In vitro, IL-1α (150pg/ml) stimulated proliferation of adolescent NPCs; IL-6 (10ng/ml) inhibited proliferation of adolescent and adult NPCs. Microarray analysis of SGZ post-TMT indicated a prominence of IL-1a/IL-1R1 signaling in the adolescent and IL-6/gp130 signaling in the adult.
McPherson
C A
CA
Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, USA.
Aoyama
M
M
Harry
G J
GJ
D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000502:physiology; D049109:Cell Proliferation; D050822:Cytokine Receptor gp130 / Q000502:physiology; D006624:Hippocampus / Q000276:immunology / Q000293:injuries* / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology*; D053582:Interleukin-1alpha / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology*; D053698:Interleukin-6 Receptor alpha Subunit / Q000502:physiology; D008297:Male; D051379:Mice; D017628:Microglia / Q000502:physiology; D058953:Neural Stem Cells / Q000502:physiology*; D053573:Receptors, Interleukin-1 Type I / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D007375:Interleukin-1; D053582:Interleukin-1alpha; D015850:Interleukin-6; D053698:Interleukin-6 Receptor alpha Subunit; D053573:Receptors, Interleukin-1 Type I; D050822:Cytokine Receptor gp130