Reciprocal changes of CD44 and GAP-43 expression in the dentate gyrus inner molecular layer after status epilepticus in mice.
Mossy fiber sprouting (MFS), a common feature of human temporal lobe epilepsy and many epilepsy animal models, contributes to hippocampal hyperexcitability. The molecular events responsible for MFS are not well understood, although the growth-associated protein GAP-43 has been implicated in rats. Here, we focus on the hyaluronan receptor CD44, which is involved in routing of retinal axons during development and is upregulated after injury in many tissues including brain. After pilocarpine-induced status epilepticus (SE) in mice most hilar neurons died and neuropeptide Y (NPY) immunoreactivity appeared in the dentate inner molecular layer (IML) after 10-31 days indicative of MFS. Strong CD44 immunoreactivity appeared in the IML 3 days after pilocarpine, then declined over the next 4 weeks. Conversely, GAP-43 immunoreactivity was decreased in the IML at 3-10 days after pilocarpine-induced SE. After SE induced by repeated kainate injections, mice did not show any hilar cell loss or changes in CD44 or GAP-43 expression in the IML, and MFS was absent at 20-35 days. Thus, after SE in mice, early loss of GAP-43 and strong CD44 induction in the IML correlated with hilar cell loss and subsequent MFS. CD44 is one of the earliest proteins upregulated in the IML and coincides with early sprouting of mossy fibers, although its function is still unknown. We hypothesize that CD44 is involved in the response to axon terminal degeneration and/or neuronal reorganization preceding MFS.
Borges
Karin
K
Department of Pharmacology, Emory University School of Medicine, Atlanta GA 30322, USA. kborges@pharm.emory.edu
McDermott
Dayna L
DL
Dingledine
Raymond
R
D000818:Animals; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019922:GAP-43 Protein / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D007608:Kainic Acid; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D010862:Pilocarpine; D013226:Status Epilepticus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
D019922:GAP-43 Protein; D018960:Hyaluronan Receptors; D009478:Neuropeptide Y; D010862:Pilocarpine; D007608:Kainic Acid