title: p75NTR, but not proNGF, is upregulated following status epilepticus in mice.
abstract: ProNGF and p75(NTR) are upregulated and induce cell death following status epilepticus (SE) in rats. However, less is known about the proneurotrophin response to SE in mice, a more genetically tractable species where mechanisms can be more readily dissected. We evaluated the temporal- and cell-specific induction of the proneurotrophins and their receptors, including p75(NTR), sortilin, and sorCS2, following mild SE induced with kainic acid (KA) or severe SE induced by pilocarpine. We found that mature NGF, p75(NTR), and proBDNF were upregulated following SE, while proNGF was not altered, indicating potential mechanistic differences between rats and mice. ProBDNF was localized to mossy fibers and microglia following SE. p75(NTR) was transiently induced primarily in axons and axon terminals following SE, as well as in neuron and astrocyte cell bodies. ProBDNF and p75(NTR) increased independently of cell death and their localization was different depending on the severity of SE. We also examined the expression of proneurotrophin co-receptors, sortilin and sorCS2. Following severe SE, sorCS2, but not sortilin, was elevated in neurons and astrocytes. These data indicate that important differences exist between rat and mouse in the proneurotrophin response following SE. Moreover, the proBDNF and p75(NTR) increase after seizures in the absence of significant cell death suggests that proneurotrophin signaling may play other roles following SE.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Melissa W
authors.initials: MW
authors.lastname: VonDran
authors.affiliation: Center of Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: John
authors.initials: J
authors.lastname: LaFrancois
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Padow
authors.affiliation: Department of Biological Sciences, Rutgers Life Sciences Center, Rutgers University, Newark, NJ, USA.
authors.forename: Wilma J
authors.initials: WJ
authors.lastname: Friedman
authors.affiliation: Center of Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Scharfman
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Milner
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY, USA Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA blhempst@med.cornell.edu.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Hempstead
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D005452:Fluoresceins; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018721:Muscarinic Agonists / Q000633:toxicity; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D005452:Fluoresceins; D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D020800:Receptor, Nerve Growth Factor; C435731:fluoro jade; C489226:pro-nerve growth factor, mouse; D010862:Pilocarpine; D020932:Nerve Growth Factor; D007608:Kainic Acid
keywords: BDNF; NGF; growth factors; p75 neurotrophin receptor; proneurotrophins; sorCS2