title: Progranulin promotes activation of microglia/macrophage after pilocarpine-induced status epilepticus.
abstract: Progranulin (PGRN) haploinsufficiency accounts for up to 10% of frontotemporal lobe dementia. PGRN has also been implicated in neuroinflammation in acute and chronic neurological disorders. Here we report that both protein and mRNA levels of cortical and hippocampal PGRN are significantly enhanced following pilocarpine-induced status epilepticus. We also identify intense PGRN immunoreactivity that colocalizes with CD11b in seizure-induced animals, suggesting that PGRN elevation occurs primarily in activated microglia and macrophages. To test the role of PGRN in activation of microglia/macrophages, we apply recombinant PGRN protein directly into the hippocampal formation, and observe no change in the number of CD11b(+) microglia/macrophages in the dentate gyrus. However, with pilocarpine-induced status epilepticus, PGRN application significantly increases the number of CD11b(+) microglia/macrophages in the dentate gyrus, without affecting the extent of hilar cell death. In addition, the number of CD11b(+) microglia/macrophages induced by status epilepticus is not significantly different between PGRN knockout mice and wildtype. Our findings suggest that status epilepticus induces PGRN expression, and that PGRN potentiates but is not required for seizure-induced microglia/macrophage activation.
authors.affiliation: Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, British Columbia, Canada. shanshanzhupku@hotmail.com
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
authors.forename: Chao
authors.initials: C
authors.lastname: Tai
authors.forename: Terri L
authors.initials: TL
authors.lastname: Petkau
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.forename: Chengyong
authors.initials: C
authors.lastname: Liao
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Dong
authors.forename: Wendy
authors.initials: W
authors.lastname: Wen
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian Wang
authors.forename: Brian A
authors.initials: BA
authors.lastname: MacVicar
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
authors.forename: William
authors.initials: W
authors.lastname: Jia
authors.forename: Max S
authors.initials: MS
authors.lastname: Cynader
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000077155:Granulins; D006624:Hippocampus / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D010862:Pilocarpine / Q000494:pharmacology; D000077153:Progranulins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
chemical_list: D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D010862:Pilocarpine
keywords: AD; ALS; Alzheimer's disease; BSA; DIV; FJB; FTLD; Frontotemporal lobe dementia; GFAP; HPLC; IL-6; KO; LPS; Microglial/macrophage activation; PGRN; Pilocarpine; Progranulin; SE; SLPI; Status epilepticus; WT; amyotrophic lateral sclerosis; bovine serum albumin; days in vitro; fluoro-Jade B; frontotemporal lobe dementia; glial fibrillary acidic protein; high performance liquid chromatography; interleukin 6; knockout; lipopolysaccharide; progranulin; secretory leukocyte protease inhibitor; status epilepticus; wildtype