Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1782518659056402432 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5372628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT behnkejoseph neuropeptidevgfpromotesmaturationofhippocampaldendritesthatisreducedbysinglenucleotidepolymorphisms AT cheedallaaneesha neuropeptidevgfpromotesmaturationofhippocampaldendritesthatisreducedbysinglenucleotidepolymorphisms AT bhattvatsal neuropeptidevgfpromotesmaturationofhippocampaldendritesthatisreducedbysinglenucleotidepolymorphisms AT bhatmaysa neuropeptidevgfpromotesmaturationofhippocampaldendritesthatisreducedbysinglenucleotidepolymorphisms AT tengshavonne neuropeptidevgfpromotesmaturationofhippocampaldendritesthatisreducedbysinglenucleotidepolymorphisms AT palmierialicia neuropeptidevgfpromotesmaturationofhippocampaldendritesthatisreducedbysinglenucleotidepolymorphisms AT windoncharleschristian neuropeptidevgfpromotesmaturationofhippocampaldendritesthatisreducedbysinglenucleotidepolymorphisms AT thakkervariasmita neuropeptidevgfpromotesmaturationofhippocampaldendritesthatisreducedbysinglenucleotidepolymorphisms AT alderjanet neuropeptidevgfpromotesmaturationofhippocampaldendritesthatisreducedbysinglenucleotidepolymorphisms |