Enhanced adult neurogenesis and angiogenesis and altered affective behaviors in mice overexpressing vascular endothelial growth factor 120

Hiroshi Udo, Yuka Yoshida, Takako Kino, Koichiro Ohnuki, Wataru Mizunoya, Takao Mukuda, Hiroyuki Sugiyama

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) is implicated as a molecular mediator for adult neurogenesis and behavioral effects of antidepressant drugs. However, these potential roles of VEGF in the CNS have not been clarified in model animals. Here we have created transgenic mice overexpressing a short active variant of VEGF-A (VEGF120) in forebrain. Expression of VEGF120 significantly enhanced cell proliferation and angiogenesis, as exemplified by the formation of an enlarged reddish brain. Adult neurogenesis in hippocampus was markedly stimulated without affecting cell differentiation of neural progenitor cells. Hippocampal neurogenesis was particularly robust in young adult animals, but it declined with age and reduced to control levels by 20 weeks under continuous expression of VEGF120. Thus, VEGF alone is not sufficient to support the long-term enhancement of adult neurogenesis, and VEGF-induced vascularization per se does not necessarily predict increased neurogenesis. In transgenic mice, we observed significant changes in affective behaviors. VEGF was found to have not only antidepressant effects but also anxiolytic effects. In addition, we found that VEGF significantly reduced fear and aggression. In contrast, basal activities under natural conditions were not affected much. Unexpectedly, these characteristic behaviors were maintained in older transgenic mice undergoing a reduced level of cell proliferation in hippocampus, suggesting that there is potential dissociation between adult neurogenesis and mood regulation. Our data indicate that VEGF exerts strong neurogenic and angiogenic effects in postnatal brain and influences different forms of affective behaviors.

Original languageEnglish
Pages (from-to)14522-14536
Number of pages15
JournalJournal of Neuroscience
Volume28
Issue number53
DOIs
Publication statusPublished - Dec 31 2008

Fingerprint

Neurogenesis
Vascular Endothelial Growth Factor A
Transgenic Mice
Antidepressive Agents
Hippocampus
Cell Proliferation
Anti-Anxiety Agents
Brain
Prosencephalon
Aggression
Fear
Cell Differentiation
Young Adult
Stem Cells
Animal Models

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Enhanced adult neurogenesis and angiogenesis and altered affective behaviors in mice overexpressing vascular endothelial growth factor 120. / Udo, Hiroshi; Yoshida, Yuka; Kino, Takako; Ohnuki, Koichiro; Mizunoya, Wataru; Mukuda, Takao; Sugiyama, Hiroyuki.

In: Journal of Neuroscience, Vol. 28, No. 53, 31.12.2008, p. 14522-14536.

Research output: Contribution to journalArticle

Udo, Hiroshi ; Yoshida, Yuka ; Kino, Takako ; Ohnuki, Koichiro ; Mizunoya, Wataru ; Mukuda, Takao ; Sugiyama, Hiroyuki. / Enhanced adult neurogenesis and angiogenesis and altered affective behaviors in mice overexpressing vascular endothelial growth factor 120. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 53. pp. 14522-14536.
@article{da3896213a694d3e96dd8544217b6686,
title = "Enhanced adult neurogenesis and angiogenesis and altered affective behaviors in mice overexpressing vascular endothelial growth factor 120",
abstract = "Vascular endothelial growth factor (VEGF) is implicated as a molecular mediator for adult neurogenesis and behavioral effects of antidepressant drugs. However, these potential roles of VEGF in the CNS have not been clarified in model animals. Here we have created transgenic mice overexpressing a short active variant of VEGF-A (VEGF120) in forebrain. Expression of VEGF120 significantly enhanced cell proliferation and angiogenesis, as exemplified by the formation of an enlarged reddish brain. Adult neurogenesis in hippocampus was markedly stimulated without affecting cell differentiation of neural progenitor cells. Hippocampal neurogenesis was particularly robust in young adult animals, but it declined with age and reduced to control levels by 20 weeks under continuous expression of VEGF120. Thus, VEGF alone is not sufficient to support the long-term enhancement of adult neurogenesis, and VEGF-induced vascularization per se does not necessarily predict increased neurogenesis. In transgenic mice, we observed significant changes in affective behaviors. VEGF was found to have not only antidepressant effects but also anxiolytic effects. In addition, we found that VEGF significantly reduced fear and aggression. In contrast, basal activities under natural conditions were not affected much. Unexpectedly, these characteristic behaviors were maintained in older transgenic mice undergoing a reduced level of cell proliferation in hippocampus, suggesting that there is potential dissociation between adult neurogenesis and mood regulation. Our data indicate that VEGF exerts strong neurogenic and angiogenic effects in postnatal brain and influences different forms of affective behaviors.",
author = "Hiroshi Udo and Yuka Yoshida and Takako Kino and Koichiro Ohnuki and Wataru Mizunoya and Takao Mukuda and Hiroyuki Sugiyama",
year = "2008",
month = "12",
day = "31",
doi = "10.1523/JNEUROSCI.3673-08.2008",
language = "English",
volume = "28",
pages = "14522--14536",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "53",

}

TY - JOUR

T1 - Enhanced adult neurogenesis and angiogenesis and altered affective behaviors in mice overexpressing vascular endothelial growth factor 120

AU - Udo, Hiroshi

AU - Yoshida, Yuka

AU - Kino, Takako

AU - Ohnuki, Koichiro

AU - Mizunoya, Wataru

AU - Mukuda, Takao

AU - Sugiyama, Hiroyuki

PY - 2008/12/31

Y1 - 2008/12/31

N2 - Vascular endothelial growth factor (VEGF) is implicated as a molecular mediator for adult neurogenesis and behavioral effects of antidepressant drugs. However, these potential roles of VEGF in the CNS have not been clarified in model animals. Here we have created transgenic mice overexpressing a short active variant of VEGF-A (VEGF120) in forebrain. Expression of VEGF120 significantly enhanced cell proliferation and angiogenesis, as exemplified by the formation of an enlarged reddish brain. Adult neurogenesis in hippocampus was markedly stimulated without affecting cell differentiation of neural progenitor cells. Hippocampal neurogenesis was particularly robust in young adult animals, but it declined with age and reduced to control levels by 20 weeks under continuous expression of VEGF120. Thus, VEGF alone is not sufficient to support the long-term enhancement of adult neurogenesis, and VEGF-induced vascularization per se does not necessarily predict increased neurogenesis. In transgenic mice, we observed significant changes in affective behaviors. VEGF was found to have not only antidepressant effects but also anxiolytic effects. In addition, we found that VEGF significantly reduced fear and aggression. In contrast, basal activities under natural conditions were not affected much. Unexpectedly, these characteristic behaviors were maintained in older transgenic mice undergoing a reduced level of cell proliferation in hippocampus, suggesting that there is potential dissociation between adult neurogenesis and mood regulation. Our data indicate that VEGF exerts strong neurogenic and angiogenic effects in postnatal brain and influences different forms of affective behaviors.

AB - Vascular endothelial growth factor (VEGF) is implicated as a molecular mediator for adult neurogenesis and behavioral effects of antidepressant drugs. However, these potential roles of VEGF in the CNS have not been clarified in model animals. Here we have created transgenic mice overexpressing a short active variant of VEGF-A (VEGF120) in forebrain. Expression of VEGF120 significantly enhanced cell proliferation and angiogenesis, as exemplified by the formation of an enlarged reddish brain. Adult neurogenesis in hippocampus was markedly stimulated without affecting cell differentiation of neural progenitor cells. Hippocampal neurogenesis was particularly robust in young adult animals, but it declined with age and reduced to control levels by 20 weeks under continuous expression of VEGF120. Thus, VEGF alone is not sufficient to support the long-term enhancement of adult neurogenesis, and VEGF-induced vascularization per se does not necessarily predict increased neurogenesis. In transgenic mice, we observed significant changes in affective behaviors. VEGF was found to have not only antidepressant effects but also anxiolytic effects. In addition, we found that VEGF significantly reduced fear and aggression. In contrast, basal activities under natural conditions were not affected much. Unexpectedly, these characteristic behaviors were maintained in older transgenic mice undergoing a reduced level of cell proliferation in hippocampus, suggesting that there is potential dissociation between adult neurogenesis and mood regulation. Our data indicate that VEGF exerts strong neurogenic and angiogenic effects in postnatal brain and influences different forms of affective behaviors.

UR - http://www.scopus.com/inward/record.url?scp=58149381563&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149381563&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.3673-08.2008

DO - 10.1523/JNEUROSCI.3673-08.2008

M3 - Article

C2 - 19118187

AN - SCOPUS:58149381563

VL - 28

SP - 14522

EP - 14536

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 53

ER -