title: Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms.
abstract: The neuropeptide VGF (non-acronymic) is induced by brain-derived neurotrophic factor and promotes hippocampal neurogenesis, as well as synaptic activity. However, morphological changes induced by VGF have not been elucidated. Developing hippocampal neurons were exposed to VGF through bath application or virus-mediated expression in vitro. VGF-derived peptide, TLQP-62, enhanced dendritic branching, and outgrowth. Furthermore, VGF increased dendritic spine density and the proportion of immature spines. Spine formation was associated with increased synaptic protein expression and co-localization of pre- and postsynaptic markers. Three non-synonymous single nucleotide polymorphisms (SNPs) were selected in humanVGFgene. Transfection of N2a cells with plasmids containing these SNPs revealed no relative change in protein expression levels and normal protein size, except for a truncated protein from the premature stop codon, E525X. All three SNPs resulted in a lower proportion of N2a cells bearing neurites relative to wild-typeVGF. Furthermore, all three mutations reduced the total length of dendrites in developing hippocampal neurons. Taken together, our results suggest VGF enhances dendritic maturation and that these effects can be altered by common mutations in theVGFgene. The findings may have implications for people suffering from psychiatric disease or other conditions who may have altered VGF levels.
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. jabehnke3@gmail.com.
authors.forename: Joseph
authors.initials: J
authors.lastname: Behnke
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. aneesha.cheedalla@gmail.com.
authors.forename: Aneesha
authors.initials: A
authors.lastname: Cheedalla
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. bhattvy@rwjms.rutgers.edu.
authors.forename: Vatsal
authors.initials: V
authors.lastname: Bhatt
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. maysa93@gmail.com.
authors.forename: Maysa
authors.initials: M
authors.lastname: Bhat
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. slt119@rwjms.rutgers.edu.
authors.forename: Shavonne
authors.initials: S
authors.lastname: Teng
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. aliciajpalmieri@gmail.com.
authors.forename: Alicia
authors.initials: A
authors.lastname: Palmieri
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. cwindon82587@gmail.com.
authors.forename: Charles Christian
authors.initials: CC
authors.lastname: Windon
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. varia@rutgers.edu.
authors.forename: Smita
authors.initials: S
authors.lastname: Thakker-Varia
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. janet.alder@rutgers.edu.
authors.forename: Janet
authors.initials: J
authors.lastname: Alder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D010455:Peptides; C000593377:TLQP62 peptide; C522413:VGF peptide
keywords: dendrite; hippocampus; neuropeptide; single nucleotide polymorphism; spine; synapse