Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-α gene

Ryuichi Iida, Kuniaki Saito, Kiyofumi Yamada, Anthony S. Basile, Kenji Sekikawa, Masao Takemura, Hidehiko Fujii, Hisayasu Wada, Mitsuru Seishima, Toshitaka Nabeshima

研究成果: Article

30 引用 (Scopus)

抄録

Brain levels of TNF-α increase in many inflammatory conditions, including HIV-1 infection, and may contribute to neurodegenerative processes. The paucity of agents that can selectively and potently block TNF-α processing or its receptors has led us to investigate the role of TNF-α in chronic neurodegeneration associated with retroviral infection using mice with targeted deletions of the TNF-α gene. Infection of wild-type C57BL/6 mice with the LP-BM5 murine leukemia retrovirus mixture leads to the development of a severe immunodeficiency as well as cognitive deficits and neuronal damage. TNFα-(-/-) mice infected with LP-BM5 developed a systemic immunopathology indistinguishable in severity from that observed in contemporaneously infected wild-type mice. In contrast, the performance of infected TNF-α-(-/-) mice in the Y-maze and Morris water maze was not different from that of uninfected TNF-α-(-/-) mice. The extent of glial activation in the striatum, as indicated by the increase in density of peripheral benzodiazepine receptors, was equivalent in both groups of LP-BM5- infected mice. However, the decrease in striatal MAP-2 expression, a marker of neurodegeneration observed in infected wild-type mice, was not found in infected TNF-α-(-/-) mice. While the loss of TNF-α appeared to have no effect on the course or severity of the central or peripheral immunopathology resulting from LP-BM5 infection, the behavioral and biochemical manifestations were substantially curtailed in the TNF-α-(-/-) mice. These findings directly support a role for TNF-α in the neurodegenerative processes associated with viral infections such as HIV-1.

元の言語English
ページ(範囲)1023-1031
ページ数9
ジャーナルFASEB Journal
14
発行部数7
出版物ステータスPublished - 16-05-2000
外部発表Yes

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Gene Deletion
GABA-A Receptors
Brain
Genes
Chemical activation
Water
Processing
HIV-1
Infection
Neuroglia
Corpus Striatum
Virus Diseases
Retroviridae
Inbred C57BL Mouse
HIV Infections
Leukemia

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

これを引用

Iida, Ryuichi ; Saito, Kuniaki ; Yamada, Kiyofumi ; Basile, Anthony S. ; Sekikawa, Kenji ; Takemura, Masao ; Fujii, Hidehiko ; Wada, Hisayasu ; Seishima, Mitsuru ; Nabeshima, Toshitaka. / Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-α gene. :: FASEB Journal. 2000 ; 巻 14, 番号 7. pp. 1023-1031.
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title = "Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-α gene",
abstract = "Brain levels of TNF-α increase in many inflammatory conditions, including HIV-1 infection, and may contribute to neurodegenerative processes. The paucity of agents that can selectively and potently block TNF-α processing or its receptors has led us to investigate the role of TNF-α in chronic neurodegeneration associated with retroviral infection using mice with targeted deletions of the TNF-α gene. Infection of wild-type C57BL/6 mice with the LP-BM5 murine leukemia retrovirus mixture leads to the development of a severe immunodeficiency as well as cognitive deficits and neuronal damage. TNFα-(-/-) mice infected with LP-BM5 developed a systemic immunopathology indistinguishable in severity from that observed in contemporaneously infected wild-type mice. In contrast, the performance of infected TNF-α-(-/-) mice in the Y-maze and Morris water maze was not different from that of uninfected TNF-α-(-/-) mice. The extent of glial activation in the striatum, as indicated by the increase in density of peripheral benzodiazepine receptors, was equivalent in both groups of LP-BM5- infected mice. However, the decrease in striatal MAP-2 expression, a marker of neurodegeneration observed in infected wild-type mice, was not found in infected TNF-α-(-/-) mice. While the loss of TNF-α appeared to have no effect on the course or severity of the central or peripheral immunopathology resulting from LP-BM5 infection, the behavioral and biochemical manifestations were substantially curtailed in the TNF-α-(-/-) mice. These findings directly support a role for TNF-α in the neurodegenerative processes associated with viral infections such as HIV-1.",
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Iida, R, Saito, K, Yamada, K, Basile, AS, Sekikawa, K, Takemura, M, Fujii, H, Wada, H, Seishima, M & Nabeshima, T 2000, 'Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-α gene', FASEB Journal, 巻. 14, 番号 7, pp. 1023-1031.

Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-α gene. / Iida, Ryuichi; Saito, Kuniaki; Yamada, Kiyofumi; Basile, Anthony S.; Sekikawa, Kenji; Takemura, Masao; Fujii, Hidehiko; Wada, Hisayasu; Seishima, Mitsuru; Nabeshima, Toshitaka.

:: FASEB Journal, 巻 14, 番号 7, 16.05.2000, p. 1023-1031.

研究成果: Article

TY - JOUR

T1 - Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-α gene

AU - Iida, Ryuichi

AU - Saito, Kuniaki

AU - Yamada, Kiyofumi

AU - Basile, Anthony S.

AU - Sekikawa, Kenji

AU - Takemura, Masao

AU - Fujii, Hidehiko

AU - Wada, Hisayasu

AU - Seishima, Mitsuru

AU - Nabeshima, Toshitaka

PY - 2000/5/16

Y1 - 2000/5/16

N2 - Brain levels of TNF-α increase in many inflammatory conditions, including HIV-1 infection, and may contribute to neurodegenerative processes. The paucity of agents that can selectively and potently block TNF-α processing or its receptors has led us to investigate the role of TNF-α in chronic neurodegeneration associated with retroviral infection using mice with targeted deletions of the TNF-α gene. Infection of wild-type C57BL/6 mice with the LP-BM5 murine leukemia retrovirus mixture leads to the development of a severe immunodeficiency as well as cognitive deficits and neuronal damage. TNFα-(-/-) mice infected with LP-BM5 developed a systemic immunopathology indistinguishable in severity from that observed in contemporaneously infected wild-type mice. In contrast, the performance of infected TNF-α-(-/-) mice in the Y-maze and Morris water maze was not different from that of uninfected TNF-α-(-/-) mice. The extent of glial activation in the striatum, as indicated by the increase in density of peripheral benzodiazepine receptors, was equivalent in both groups of LP-BM5- infected mice. However, the decrease in striatal MAP-2 expression, a marker of neurodegeneration observed in infected wild-type mice, was not found in infected TNF-α-(-/-) mice. While the loss of TNF-α appeared to have no effect on the course or severity of the central or peripheral immunopathology resulting from LP-BM5 infection, the behavioral and biochemical manifestations were substantially curtailed in the TNF-α-(-/-) mice. These findings directly support a role for TNF-α in the neurodegenerative processes associated with viral infections such as HIV-1.

AB - Brain levels of TNF-α increase in many inflammatory conditions, including HIV-1 infection, and may contribute to neurodegenerative processes. The paucity of agents that can selectively and potently block TNF-α processing or its receptors has led us to investigate the role of TNF-α in chronic neurodegeneration associated with retroviral infection using mice with targeted deletions of the TNF-α gene. Infection of wild-type C57BL/6 mice with the LP-BM5 murine leukemia retrovirus mixture leads to the development of a severe immunodeficiency as well as cognitive deficits and neuronal damage. TNFα-(-/-) mice infected with LP-BM5 developed a systemic immunopathology indistinguishable in severity from that observed in contemporaneously infected wild-type mice. In contrast, the performance of infected TNF-α-(-/-) mice in the Y-maze and Morris water maze was not different from that of uninfected TNF-α-(-/-) mice. The extent of glial activation in the striatum, as indicated by the increase in density of peripheral benzodiazepine receptors, was equivalent in both groups of LP-BM5- infected mice. However, the decrease in striatal MAP-2 expression, a marker of neurodegeneration observed in infected wild-type mice, was not found in infected TNF-α-(-/-) mice. While the loss of TNF-α appeared to have no effect on the course or severity of the central or peripheral immunopathology resulting from LP-BM5 infection, the behavioral and biochemical manifestations were substantially curtailed in the TNF-α-(-/-) mice. These findings directly support a role for TNF-α in the neurodegenerative processes associated with viral infections such as HIV-1.

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Iida R, Saito K, Yamada K, Basile AS, Sekikawa K, Takemura M その他. Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-α gene. FASEB Journal. 2000 5 16;14(7):1023-1031.