title: Anti-Mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin.
abstract: The balance between tissue-type plasminogen activator (tPA) and one of its inhibitors, neuroserpin, has crucial roles in the central nervous system, including the control of neuronal migration, neuronal plasticity and neuronal death. In the present study, we demonstrate that the activation of the transforming growth factor-beta (TGFbeta)-related BMPR-IB (also known as BMPR1B and Alk6)- and Smad5-dependent signalling pathways controls neuroserpin transcription. Accordingly, we demonstrate for the first time that anti-Mullerian hormone (AMH), a member of the TGFbeta family, promotes the expression of neuroserpin in cultured neurons but not in astrocytes. The relevance of these findings is confirmed by the presence of both AMH and AMH type-II receptor (AMHR-II) in brain tissues, and is supported by the observation of reduced levels of neuroserpin in the brain of AMHR-II-deficient mice. Interestingly, as previously demonstrated for neuroserpin, AMH protects neurons against N-methyl-D-aspartate (NMDA)-mediated excitotoxicity both in vitro and in vivo. This study demonstrates the existence of an AMH-dependent signalling pathway in the brain leading to an overexpression of the serine-protease inhibitor, neuroserpin, and neuronal survival.
authors.affiliation: INSERM, INSERM U919, Serine Proteases and Pathophysiology of the neurovascular Unit (SP2U), Cyceron, F-14074 France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lebeurrier
authors.forename: Séverine
authors.initials: S
authors.lastname: Launay
authors.forename: Richard
authors.initials: R
authors.lastname: Macrez
authors.forename: Eric
authors.initials: E
authors.lastname: Maubert
authors.forename: Hélène
authors.initials: H
authors.lastname: Legros
authors.forename: Arnaud
authors.initials: A
authors.lastname: Leclerc
authors.forename: Soazik P
authors.initials: SP
authors.lastname: Jamin
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Picard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marret
authors.forename: Vincent
authors.initials: V
authors.lastname: Laudenbach
authors.forename: Philipp
authors.initials: P
authors.lastname: Berger
authors.forename: Peter
authors.initials: P
authors.lastname: Sonderegger
authors.forename: Carine
authors.initials: C
authors.lastname: Ali
authors.forename: Nathalie
authors.initials: N
authors.lastname: di Clemente
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051902:Smad5 Protein / Q000235:genetics / Q000378:metabolism; D000097522:Neuroserpin
chemical_list: D054304:Anti-Mullerian Hormone; D052005:Bone Morphogenetic Protein Receptors, Type I; D009479:Neuropeptides; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D015843:Serpins; D051902:Smad5 Protein; D000097522:Neuroserpin; C497798:Smad5 protein, mouse; C084621:anti-Mullerian hormone receptor; C498215:Bmpr1b protein, mouse