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PMID: 15056704 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A transgenic marker for newly born granule cells in dentate gyrus.

Overstreet LS, Hentges ST, Bumaschny VF, de Souza FS, Smart JL, Santangelo AM, Low MJ, Westbrook GL, Rubinstein M

Abstract

Neurogenesis in the dentate gyrus continues into adulthood, yet little is known about the function of newly born neurons or how they integrate into an existing network of mature neurons. We made transgenic mice that selectively and transiently express enhanced green fluorescent protein (EGFP) in newly born granule cells of the dentate gyrus under the transcriptional control of proopiomelanocortin (POMC) genomic sequences. Analysis of transgenic pedigrees with truncation or deletion mutations indicated that EGFP expression in the dentate gyrus required cryptic POMC promoter regions dispensable for arcuate hypothalamic or pituitary expression. Unlike arcuate neurons, dentate granule cells did not express the endogenous POMC gene. EGFP-positive neurons had immature properties, including short spineless dendrites and small action potentials. Colocalization with bromodeoxyuridine indicated that EGFP-labeled granule cells were approximately 2 weeks postmitotic. EGFP-labeled cells expressed markers for immature granule cells but not the glial marker GFAP. The number of EGFP-labeled neurons declined with age and increased with exercise, paralleling neurogenesis. Our results indicate that POMC-EGFP marks immature granule cells and that adult-generated granule cells integrate quite slowly into the hippocampal circuitry.

MeSH Terms
Action Potentials/physiology Aging/metabolism Animals Biomarkers/analysis Bromodeoxyuridine Cell Count Cell Division/physiology Cell Movement Dentate Gyrus/cytology,metabolism Genes, Reporter Green Fluorescent Proteins Luminescent Proteins/biosynthesis,genetics Mice Mice, Inbred C57BL Mice, Transgenic Neural Cell Adhesion Molecule L1/biosynthesis Neurons/metabolism Physical Exertion/physiology Pro-Opiomelanocortin/genetics Promoter Regions, Genetic/physiology Sialic Acids/biosynthesis Transgenes/physiology
Chemicals
Biomarkers Luminescent Proteins Neural Cell Adhesion Molecule L1 Sialic Acids polysialyl neural cell adhesion molecule Green Fluorescent Proteins Pro-Opiomelanocortin Bromodeoxyuridine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Overstreet Linda S
Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. [email protected]
Hentges Shane T
Bumaschny Viviana F
de Souza Flavio S J
Smart James L
Santangelo Andrea M
Low Malcolm J
Westbrook Gary L
Rubinstein Marcelo
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2004-03-31
Pages
3251-9
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6730035
Subset
IM
Grants
NIDDK NIH HHS · R01 DK066604 · United States
NIDDK NIH HHS · P01 DK055819 · United States
NINDS NIH HHS · R01 NS026494 · United States
NIDDK NIH HHS · DK55819 · United States
NINDS NIH HHS · NS26494 · United States
FIC NIH HHS · R03 TW001233 · United States
FIC NIH HHS · TW01233 · United States
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