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Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms

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 applicatio...

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Autores principales: Behnke, Joseph, Cheedalla, Aneesha, Bhatt, Vatsal, Bhat, Maysa, Teng, Shavonne, Palmieri, Alicia, Windon, Charles Christian, Thakker-Varia, Smita, Alder, Janet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372628/
https://www.ncbi.nlm.nih.gov/pubmed/28287464
http://dx.doi.org/10.3390/ijms18030612
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author Behnke, Joseph
Cheedalla, Aneesha
Bhatt, Vatsal
Bhat, Maysa
Teng, Shavonne
Palmieri, Alicia
Windon, Charles Christian
Thakker-Varia, Smita
Alder, Janet
author_facet Behnke, Joseph
Cheedalla, Aneesha
Bhatt, Vatsal
Bhat, Maysa
Teng, Shavonne
Palmieri, Alicia
Windon, Charles Christian
Thakker-Varia, Smita
Alder, Janet
author_sort Behnke, Joseph
collection PubMed
description 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 human VGF gene. 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-type VGF. 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 the VGF gene. The findings may have implications for people suffering from psychiatric disease or other conditions who may have altered VGF levels.
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spelling pubmed-53726282017-04-10 Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms Behnke, Joseph Cheedalla, Aneesha Bhatt, Vatsal Bhat, Maysa Teng, Shavonne Palmieri, Alicia Windon, Charles Christian Thakker-Varia, Smita Alder, Janet Int J Mol Sci Article 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 human VGF gene. 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-type VGF. 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 the VGF gene. The findings may have implications for people suffering from psychiatric disease or other conditions who may have altered VGF levels. MDPI 2017-03-11 /pmc/articles/PMC5372628/ /pubmed/28287464 http://dx.doi.org/10.3390/ijms18030612 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Behnke, Joseph
Cheedalla, Aneesha
Bhatt, Vatsal
Bhat, Maysa
Teng, Shavonne
Palmieri, Alicia
Windon, Charles Christian
Thakker-Varia, Smita
Alder, Janet
Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms
title Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms
title_full Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms
title_fullStr Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms
title_full_unstemmed Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms
title_short Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms
title_sort neuropeptide vgf promotes maturation of hippocampal dendrites that is reduced by single nucleotide polymorphisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372628/
https://www.ncbi.nlm.nih.gov/pubmed/28287464
http://dx.doi.org/10.3390/ijms18030612
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