Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus- mediated gene transfer in normal gerbil hippocampus and ventricle

H. Kitagawa, Y. Setoguchi, Y. Fukuchi, Y. Mitsumoto, N. Koga, T. Mori, Koji Abe

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Foreign genes have been successfully transferred and expressed in experimental animal brains using adenoviral vectors. However, it is not fully understood whether adenovirus-mediated gene transfer causes stressful or cytotoxic injury in brain. A replication-defective adenoviral vector containing the Escherichia coli lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral ventricle of normal gerbil brains. Temporal and spatial profiles of the expression of lacZ gene products, DNA fragmentation detected by terminal deoxynucleotidyl d-UTP nick end labeling (TUNEL) staining, and heat shock protein 72 (HSP72) immunoreactivity were examined until 21 days after the injection. In the ventricle, lacZ gene was immediately and strongly expressed at 8 hr after the injection of AdCMVnLacZ, with a peak at 1-3 days, and disappeared by 21 days. Although a small number of choroid plexus cells were TUNEL positive at 3 and 7 days, no HSP72 immunostaining was observed in the ventricle. Small-to-moderate expression of lacZ gene was found in the needle route from 8 hr to 3 days after the injection, and a small number of TUNEL-positive cells were detected at the needle track at 1-3 days. In the hippocampus, lacZ gene was markedly expressed around the dentate gyrus (DG) at 8 hr to 3 days with a peak at 1 day. Large number of TUNEL or moderate-to-dense HSP70 staining cells were also detected in the same area. CA1 neuronal cells just adjacent to the needle route showed TUNEL positivity at 1 to 3 days. However, the TUNEL staining was not associated with lacZ gene expression. The majority of lacZ- expressing cells were discriminated from the TUNEL-positive cells, whereas some were double-positive with HSP72 staining in DG. Cellular loss was observed in the CA1 layer around the needle route. An apoptotic change was morphologically observed in the marginal region of the DG at 1-3 days and in the ventricle at 3-7 days. In the sham control group, TUNEL-positive or HSP72-staining cells were only detected around the needle track including CA1 cells adjacent to the needle route. These data suggest that adenoviral gene transfer may induce direct traumatic injury in the CA1 sector near the needle route, indirect apoptotic cell loss in the DG and ventricle, and stressful effect on the dentate granule cells in association with adenovirus infection in normal gerbil brain.

Original languageEnglish
Pages (from-to)38-45
Number of pages8
JournalJournal of Neuroscience Research
Volume54
Issue number1
DOIs
Publication statusPublished - Oct 1 1998

Fingerprint

HSP72 Heat-Shock Proteins
Gerbillinae
DNA Fragmentation
Uridine Triphosphate
Adenoviridae
Hippocampus
Lac Operon
Needles
Genes
Dentate Gyrus
Staining and Labeling
Injections
Brain
Adenoviridae Infections
Choroid Plexus
Lateral Ventricles
Brain Injuries
Heart Ventricles

Keywords

  • Adenovirus
  • Apoptosis
  • LacZ gene
  • Necrosis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus- mediated gene transfer in normal gerbil hippocampus and ventricle. / Kitagawa, H.; Setoguchi, Y.; Fukuchi, Y.; Mitsumoto, Y.; Koga, N.; Mori, T.; Abe, Koji.

In: Journal of Neuroscience Research, Vol. 54, No. 1, 01.10.1998, p. 38-45.

Research output: Contribution to journalArticle

Kitagawa, H. ; Setoguchi, Y. ; Fukuchi, Y. ; Mitsumoto, Y. ; Koga, N. ; Mori, T. ; Abe, Koji. / Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus- mediated gene transfer in normal gerbil hippocampus and ventricle. In: Journal of Neuroscience Research. 1998 ; Vol. 54, No. 1. pp. 38-45.
@article{cf8457c2a7fb426d8aa84ef5951ad847,
title = "Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus- mediated gene transfer in normal gerbil hippocampus and ventricle",
abstract = "Foreign genes have been successfully transferred and expressed in experimental animal brains using adenoviral vectors. However, it is not fully understood whether adenovirus-mediated gene transfer causes stressful or cytotoxic injury in brain. A replication-defective adenoviral vector containing the Escherichia coli lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral ventricle of normal gerbil brains. Temporal and spatial profiles of the expression of lacZ gene products, DNA fragmentation detected by terminal deoxynucleotidyl d-UTP nick end labeling (TUNEL) staining, and heat shock protein 72 (HSP72) immunoreactivity were examined until 21 days after the injection. In the ventricle, lacZ gene was immediately and strongly expressed at 8 hr after the injection of AdCMVnLacZ, with a peak at 1-3 days, and disappeared by 21 days. Although a small number of choroid plexus cells were TUNEL positive at 3 and 7 days, no HSP72 immunostaining was observed in the ventricle. Small-to-moderate expression of lacZ gene was found in the needle route from 8 hr to 3 days after the injection, and a small number of TUNEL-positive cells were detected at the needle track at 1-3 days. In the hippocampus, lacZ gene was markedly expressed around the dentate gyrus (DG) at 8 hr to 3 days with a peak at 1 day. Large number of TUNEL or moderate-to-dense HSP70 staining cells were also detected in the same area. CA1 neuronal cells just adjacent to the needle route showed TUNEL positivity at 1 to 3 days. However, the TUNEL staining was not associated with lacZ gene expression. The majority of lacZ- expressing cells were discriminated from the TUNEL-positive cells, whereas some were double-positive with HSP72 staining in DG. Cellular loss was observed in the CA1 layer around the needle route. An apoptotic change was morphologically observed in the marginal region of the DG at 1-3 days and in the ventricle at 3-7 days. In the sham control group, TUNEL-positive or HSP72-staining cells were only detected around the needle track including CA1 cells adjacent to the needle route. These data suggest that adenoviral gene transfer may induce direct traumatic injury in the CA1 sector near the needle route, indirect apoptotic cell loss in the DG and ventricle, and stressful effect on the dentate granule cells in association with adenovirus infection in normal gerbil brain.",
keywords = "Adenovirus, Apoptosis, LacZ gene, Necrosis",
author = "H. Kitagawa and Y. Setoguchi and Y. Fukuchi and Y. Mitsumoto and N. Koga and T. Mori and Koji Abe",
year = "1998",
month = "10",
day = "1",
doi = "10.1002/(SICI)1097-4547(19981001)54:1<38::AID-JNR5>3.0.CO;2-I",
language = "English",
volume = "54",
pages = "38--45",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus- mediated gene transfer in normal gerbil hippocampus and ventricle

AU - Kitagawa, H.

AU - Setoguchi, Y.

AU - Fukuchi, Y.

AU - Mitsumoto, Y.

AU - Koga, N.

AU - Mori, T.

AU - Abe, Koji

PY - 1998/10/1

Y1 - 1998/10/1

N2 - Foreign genes have been successfully transferred and expressed in experimental animal brains using adenoviral vectors. However, it is not fully understood whether adenovirus-mediated gene transfer causes stressful or cytotoxic injury in brain. A replication-defective adenoviral vector containing the Escherichia coli lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral ventricle of normal gerbil brains. Temporal and spatial profiles of the expression of lacZ gene products, DNA fragmentation detected by terminal deoxynucleotidyl d-UTP nick end labeling (TUNEL) staining, and heat shock protein 72 (HSP72) immunoreactivity were examined until 21 days after the injection. In the ventricle, lacZ gene was immediately and strongly expressed at 8 hr after the injection of AdCMVnLacZ, with a peak at 1-3 days, and disappeared by 21 days. Although a small number of choroid plexus cells were TUNEL positive at 3 and 7 days, no HSP72 immunostaining was observed in the ventricle. Small-to-moderate expression of lacZ gene was found in the needle route from 8 hr to 3 days after the injection, and a small number of TUNEL-positive cells were detected at the needle track at 1-3 days. In the hippocampus, lacZ gene was markedly expressed around the dentate gyrus (DG) at 8 hr to 3 days with a peak at 1 day. Large number of TUNEL or moderate-to-dense HSP70 staining cells were also detected in the same area. CA1 neuronal cells just adjacent to the needle route showed TUNEL positivity at 1 to 3 days. However, the TUNEL staining was not associated with lacZ gene expression. The majority of lacZ- expressing cells were discriminated from the TUNEL-positive cells, whereas some were double-positive with HSP72 staining in DG. Cellular loss was observed in the CA1 layer around the needle route. An apoptotic change was morphologically observed in the marginal region of the DG at 1-3 days and in the ventricle at 3-7 days. In the sham control group, TUNEL-positive or HSP72-staining cells were only detected around the needle track including CA1 cells adjacent to the needle route. These data suggest that adenoviral gene transfer may induce direct traumatic injury in the CA1 sector near the needle route, indirect apoptotic cell loss in the DG and ventricle, and stressful effect on the dentate granule cells in association with adenovirus infection in normal gerbil brain.

AB - Foreign genes have been successfully transferred and expressed in experimental animal brains using adenoviral vectors. However, it is not fully understood whether adenovirus-mediated gene transfer causes stressful or cytotoxic injury in brain. A replication-defective adenoviral vector containing the Escherichia coli lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral ventricle of normal gerbil brains. Temporal and spatial profiles of the expression of lacZ gene products, DNA fragmentation detected by terminal deoxynucleotidyl d-UTP nick end labeling (TUNEL) staining, and heat shock protein 72 (HSP72) immunoreactivity were examined until 21 days after the injection. In the ventricle, lacZ gene was immediately and strongly expressed at 8 hr after the injection of AdCMVnLacZ, with a peak at 1-3 days, and disappeared by 21 days. Although a small number of choroid plexus cells were TUNEL positive at 3 and 7 days, no HSP72 immunostaining was observed in the ventricle. Small-to-moderate expression of lacZ gene was found in the needle route from 8 hr to 3 days after the injection, and a small number of TUNEL-positive cells were detected at the needle track at 1-3 days. In the hippocampus, lacZ gene was markedly expressed around the dentate gyrus (DG) at 8 hr to 3 days with a peak at 1 day. Large number of TUNEL or moderate-to-dense HSP70 staining cells were also detected in the same area. CA1 neuronal cells just adjacent to the needle route showed TUNEL positivity at 1 to 3 days. However, the TUNEL staining was not associated with lacZ gene expression. The majority of lacZ- expressing cells were discriminated from the TUNEL-positive cells, whereas some were double-positive with HSP72 staining in DG. Cellular loss was observed in the CA1 layer around the needle route. An apoptotic change was morphologically observed in the marginal region of the DG at 1-3 days and in the ventricle at 3-7 days. In the sham control group, TUNEL-positive or HSP72-staining cells were only detected around the needle track including CA1 cells adjacent to the needle route. These data suggest that adenoviral gene transfer may induce direct traumatic injury in the CA1 sector near the needle route, indirect apoptotic cell loss in the DG and ventricle, and stressful effect on the dentate granule cells in association with adenovirus infection in normal gerbil brain.

KW - Adenovirus

KW - Apoptosis

KW - LacZ gene

KW - Necrosis

UR - http://www.scopus.com/inward/record.url?scp=0032189267&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032189267&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-4547(19981001)54:1<38::AID-JNR5>3.0.CO;2-I

DO - 10.1002/(SICI)1097-4547(19981001)54:1<38::AID-JNR5>3.0.CO;2-I

M3 - Article

C2 - 9778148

AN - SCOPUS:0032189267

VL - 54

SP - 38

EP - 45

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 1

ER -