title: NT-3 protein levels are enhanced in the hippocampus of PRG1-deficient mice but remain unchanged in PRG1/LPA2 double mutants.
abstract: The plasticity-related gene 1 (PRG1) modulates bioactive lipids at the postsynaptic density and is a novel player in neuronal plasticity and regulation of glutamatergic transmission at principal neurons. PRG1, a neuronal molecule, is highly expressed during development and regeneration processes at the postsynaptic density, modulates synaptic lysophosphatidic acid (LPA) levels and is related to epilepsy and brain injury. In the present study, we analyzed the interaction between the synaptic molecules PRG1 and LPA2R with other plasticity-related molecules the neurotrophins. The protein levels of NGF, BDNF and NT-3 were measured using ELISA in hippocampal tissue of homozygous (PRG(-/-)) and heterozygous (PRG(+/-)) PRG1 deficient mice and compared to their wild type (PRG(+/+)/WT) littermates. In the hippocampus, protein levels of NT-3 were significantly increased in PRG(-/-) mice (compared to WT-litters) while protein levels of NGF and BDNF were not affected. Since PRG1 deficiency leads to increased neuronal excitability and higher hippocampal network activity, which may well influence neurotrophin levels, we further assessed PRG1 deficient mice on an LPA2-receptor (LPA2R) deficient background, reported to normalize hippocampal over-excitability in PRG1(-/-) mice. However, on an LPA2R deficient background, protein levels of NT-3 in PRG1(-/-) mice (PRG1(-/-)/LPA2R(-/-)) were not significantly different when compared to WT animals. Since PRG1 deficient mice showed over-excitability in glutamatergic neurons. This was normalized by additional LPA2R deletion, and we conclude the increased NT3-levels were directly or indirectly attributable to increased hippocampal network activity, possibly exerting a protective effect against over-excitability.
authors.affiliation: Institute of Anatomy, Medical Faculty Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Petzold
authors.affiliation: Institute of Anatomy, Medical Faculty Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Babette
authors.initials: B
authors.lastname: Sommer
authors.affiliation: Institute of Anatomy, Medical Faculty Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kröber
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
authors.affiliation: Institute of Anatomy, Medical Faculty Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwegler
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Vogt
authors.affiliation: Institute of Anatomy, Medical Faculty Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. Electronic address: thomas.roskoden@med.ovgu.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roskoden
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D010711:Phosphatidate Phosphatase / Q000235:genetics*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*; D013569:Synapses / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D049368:Receptors, Lysophosphatidic Acid; C518911:neurotropin 3, mouse; D020932:Nerve Growth Factor; C112948:lipid phosphate phosphatase; D010711:Phosphatidate Phosphatase
keywords: Hippocampus; Lysophosphatidic acid 2 receptor (LPA2R); Mouse; Neurotrophic factors; Plasticity-related gene 1 (PRG1)