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VGF (TLQP-62)-induced Neurogenesis Targets Early Phase Neural Progenitor Cells in the Adult Hippocampus and Requires Glutamate and BDNF Signaling

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Text
TitleInfo
Title
VGF (TLQP-62)-induced Neurogenesis Targets Early Phase Neural Progenitor Cells in the Adult Hippocampus and Requires Glutamate and BDNF Signaling
Name (type = corporate); (authority = RutgersOrg-Department)
NamePart
Neuroscience and Cell Biology
Name (type = corporate); (authority = RutgersOrg-School)
NamePart
Robert Wood Johnson Medical School (RWJMS)
Genre (authority = RULIB-FS)
Article, Non-refereed
Genre (authority = NISO JAV)
Version of Record (VoR)
OriginInfo
DateIssued (encoding = w3cdtf); (qualifier = exact); (keyDate = yes)
2014
Abstract (type = Abstract)
The neuropeptide VGF (non-acronymic), which has antidepressant-like effects, enhances adult hippocampal neurogenesis as well as synaptic activity and plasticity in the hippocampus, however the interaction between these processes and the mechanism underlying this regulation remain unclear. In this study, we demonstrate that VGF-derived peptide TLQP-62 specifically enhances the generation of early progenitor cells in nestin-GFP mice. Specifically, TLQP-62 significantly increases the number of Type 2a neural progenitor cells (NPCs) while reducing the number of more differentiated Type 3 cells. The effect of TLQP-62 on proliferation rather than differentiation was confirmed using NPCs in vitro; TLQP-62 but not scrambled peptide PEHN-62 increases proliferation in a cell line as well as in primary progenitors from adult hippocampus. Moreover, TLQP-62 but not scrambled peptide increases Cyclin D mRNA expression. The proliferation of NPCs induced by TLQP-62 requires synaptic activity, in particular through NMDA and metabotropic glutamate receptors. The activation of glutamate receptors by TLQP-62 activation induces phosphorylation of CaMKII through NMDA receptors and protein kinase D through metabotropic glutamate receptor 5 (mGluR5). Furthermore, pharmacological antagonists to CaMKII and PKD inhibit TLQP-62-induced proliferation of NPCs indicating that these signaling molecules downstream of glutamate receptors are essential for the actions of TLQP-62 on neurogenesis. We also show that TLQP-62 gradually activates Brain-Derived Neurotrophic Factor (BDNF)-receptor TrkB in vitro and that Trk signaling is required for TLQP-62- induced proliferation of NPCs. Understanding the precise molecular mechanism of how TLQP-62 influences neurogenesis may reveal mechanisms by which VGF-derived peptides act as antidepressantlike agents.
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
PhysicalDescription
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application/pdf
Extent
16 p.
Extension
DescriptiveEvent
Type
Citation
DateTime (encoding = w3cdtf)
2014
AssociatedObject
Name
Stem Cell Research
Type
Journal
Relationship
Has part
Detail
762-777
Identifier (type = volume and issue)
12(3)
Reference (type = url)
https://dx.doi.org/10.1016/j.scr.2014.03.005
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
National Institutes of Health
AssociatedEntity
Role
Originator
Subject (authority = LCSH)
Topic
Peptides
Subject (authority = local)
Topic
TLQP-62
Subject (authority = local)
Topic
Neural progenitor cells
Subject (authority = LCSH)
Topic
Stem cells
Subject (authority = LCSH)
Topic
Developmental neurobiology
Subject (authority = LCSH)
Topic
Antidepressants
Name (type = personal)
NamePart (type = family)
Thakker-Varia
NamePart (type = given)
Smita
Affiliation
Neuroscience and Cell Biology, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Behnke
NamePart (type = given)
Joseph
Affiliation
Neuroscience and Cell Biology, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Doobin
NamePart (type = given)
David
Affiliation
Neuroscience and Cell Biology, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Dalal
NamePart (type = given)
Vidhi
Affiliation
Neuroscience and Cell Biology, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Thakkar
NamePart (type = given)
Keya
Affiliation
Neuroscience and Cell Biology, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Khadim
NamePart (type = given)
Farah
Affiliation
Neuroscience and Cell Biology, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Wilson
NamePart (type = given)
Elizabeth
Affiliation
Neuroscience and Cell Biology, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Palmieri
NamePart (type = given)
Alicia
Affiliation
Neuroscience and Cell Biology, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Antila
NamePart (type = given)
Hanna
Affiliation
University of Helsinki
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Rantamaki
NamePart (type = given)
Tomi
Affiliation
University of Helsinki
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal); (authority = orcid); (authorityURI = http://id.loc.gov/vocabulary/identifiers/orcid.html); (valueURI = http://orcid.org/0000-0002-5694-4946)
NamePart (type = family)
Alder
NamePart (type = given)
Janet
Affiliation
Neuroscience and Cell Biology, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
RelatedItem (type = host)
TitleInfo
Title
Thakker-Varia, Smita
Identifier (type = local)
rucore30188900001
Note
© 2014. This manuscript version is made available under the CC-BY-NC-ND 3.0 license http://creativecommons.org/licenses/by-nc-nd/3.0/
Note (type = peerReview)
Peer reviewed
RelatedItem (type = host)
TitleInfo
Title
Alder, Janet
Identifier (type = local)
rucore30160300001
RelatedItem (type = host)
TitleInfo
Title
Thakker-Varia, Smita
Identifier (type = local)
rucore30188900001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3862JFV
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© 2014. This manuscript version is made available under the CC-BY-NC-ND 3.0 license http://creativecommons.org/licenses/by-nc-nd/3.0/
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