title: Inhibition of Protease-Activated Receptor 1 Does not Affect Dendritic Homeostasis of Cultured Mouse Dentate Granule Cells.
abstract: Protease-activated receptors (PARs) are widely expressed in the central nervous system (CNS). While a firm link between PAR1-activation and functional synaptic and intrinsic neuronal properties exists, studies on the role of PAR1 in neural structural plasticity are scarce. The physiological function of PAR1 in the brain remains not well understood. We here sought to determine whether prolonged pharmacologic PAR1-inhibition affects dendritic morphologies of hippocampal neurons. To address this question we employed live-cell microscopy of mouse dentate granule cell dendrites in 3-week old entorhino-hippocampal slice cultures prepared from Thy1-GFP mice. A subset of cultures were treated with the PAR1-inhibitor SCH79797 (1 μM; up to 3 weeks). No major effects of PAR1-inhibition on static and dynamic parameters of dentate granule cell dendrites were detected under control conditions. Granule cells of PAR1-deficient slice cultures showed unaltered dendritic morphologies, dendritic spine densities and excitatory synaptic strength. Furthermore, we report that PAR1-inhibition does not prevent dendritic retraction following partial deafferentation in vitro. Consistent with this finding, no major changes in PAR1-mRNA levels were detected in the denervated dentate gyrus (DG). We conclude that neural PAR1 is not involved in regulating the steady-state dynamics or deafferentation-induced adaptive changes of cultured dentate granule cell dendrites. These results indicate that drugs targeting neural PAR1-signals may not affect the stability and structural integrity of neuronal networks in healthy brain regions.
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt Frankfurt, Germany.
authors.forename: Gerlind
authors.initials: G
authors.lastname: Schuldt
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt Frankfurt, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Galanis
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strehl
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt Frankfurt, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Hick
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt Frankfurt, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schiener
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University FrankfurtFrankfurt, Germany; Institute of Anatomy II, Faculty of Medicine, Heinrich-Heine-University DüsseldorfDüsseldorf, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Lenz
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt Frankfurt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Deller
authors.affiliation: Department of Neurology, The Sagol Center for Neurosciences, Sheba Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv UniversityTel Aviv, Israel; Talpiot Medical Leadership Program, Department of Neurology and J. Sagol Neuroscience Center, The Chaim Sheba Medical CenterTel HaShomer, Israel; Sagol School of Neuroscience, Tel Aviv UniversityTel Aviv, Israel.
authors.forename: Nicola
authors.initials: N
authors.lastname: Maggio
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University FrankfurtFrankfurt, Germany; Institute of Anatomy II, Faculty of Medicine, Heinrich-Heine-University DüsseldorfDüsseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Vlachos
keywords: brain injury; coagulation; entorhinal cortex lesion; hippocampus; thrombin