• Shanshan Zhu, Chao Tai, Terri L Petkau, Si Zhang, Chengyong Liao, Zhifang Dong, Wendy Wen, Qing Chang, Yu Tian Wang, Brian A MacVicar, Blair R Leavitt, William Jia, and Max S Cynader.
• Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, British Columbia, Canada. shanshanzhupku@hotmail.com
• Brain Res. 2013 Sep 12;1530:54-65.

AbstractProgranulin (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.Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved.

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