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Interferon-gamma plus lipopolysaccharide induction of delayed neuronal apoptosis in rat hippocampus.

Abstract

Interferon-gamma and lipopolysaccharide (IFN-gamma/LPS) induce expression of inducible nitric oxide synthase (iNOS) protein both in cells in vitro and in the brain in vivo. In cultured cells, excessive production of nitric oxide (NO) induces neuronal cell death. However, it is still unclear whether IFN-gamma and LPS might induce neuronal cell death in vivo. In this study, we examined the neuronal cell death and induction of major histocompatibility complex (MHC) antigens after microinjection of IFN-gamma/LPS into the rat hippocampus. Although microglia appeared morphologically ramified in the normal and vehicle-injected hippocampus, microinjection of IFN-gamma/LPS immediately induced the ameboid type. From days 1-7, iNOS was expressed in ameboid microglia surrounding the site of the microinjection. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells appeared among the granular neurons of the dentate gyrus on day 3 and peaked about 7 days after microinjection. When the NOS inhibitor N(G)-nitro-L-arginine (L-NA) was intraperitoneally administered prior to the microinjection, the number of TUNEL-positive neurons decreased in a L-NA dose-dependent manner. These results suggest that IFN-gamma/LPS induces delayed neuronal apoptosis in the hippocampus in vivo, and it possibly involves excessive NO production by iNOS. Thus, this animal model may be one of neurodegenerative with extensive inflammatory activation in the hippocampus.

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  • Authors+Show Affiliations

    ,

    Department of Neurobiology, Kyoto Pharmaceutical University, Yamashina, Japan. myasuji-ind@umin.ac.jp

    , , , , , ,

    Source

    Neurochemistry international 34:2 1999 Feb pg 91-9

    MeSH

    Animals
    Apoptosis
    Cells, Cultured
    Enzyme Induction
    Enzyme Inhibitors
    Glial Fibrillary Acidic Protein
    Hippocampus
    Histocompatibility Antigens Class I
    Histocompatibility Antigens Class II
    Immunohistochemistry
    In Situ Nick-End Labeling
    Interferon-gamma
    Lipopolysaccharides
    Macrophage-1 Antigen
    Male
    Neurons
    Nitric Oxide Synthase
    Nitric Oxide Synthase Type II
    Nitroarginine
    Rats
    Rats, Wistar

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    10213066

    Citation

    Matsuoka, Y, et al. "Interferon-gamma Plus Lipopolysaccharide Induction of Delayed Neuronal Apoptosis in Rat Hippocampus." Neurochemistry International, vol. 34, no. 2, 1999, pp. 91-9.
    Matsuoka Y, Kitamura Y, Takahashi H, et al. Interferon-gamma plus lipopolysaccharide induction of delayed neuronal apoptosis in rat hippocampus. Neurochem Int. 1999;34(2):91-9.
    Matsuoka, Y., Kitamura, Y., Takahashi, H., Tooyama, I., Kimura, H., Gebicke-Haerter, P. J., ... Taniguchi, T. (1999). Interferon-gamma plus lipopolysaccharide induction of delayed neuronal apoptosis in rat hippocampus. Neurochemistry International, 34(2), pp. 91-9.
    Matsuoka Y, et al. Interferon-gamma Plus Lipopolysaccharide Induction of Delayed Neuronal Apoptosis in Rat Hippocampus. Neurochem Int. 1999;34(2):91-9. PubMed PMID: 10213066.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Interferon-gamma plus lipopolysaccharide induction of delayed neuronal apoptosis in rat hippocampus. AU - Matsuoka,Y, AU - Kitamura,Y, AU - Takahashi,H, AU - Tooyama,I, AU - Kimura,H, AU - Gebicke-Haerter,P J, AU - Nomura,Y, AU - Taniguchi,T, PY - 1999/4/23/pubmed PY - 1999/4/23/medline PY - 1999/4/23/entrez SP - 91 EP - 9 JF - Neurochemistry international JO - Neurochem. Int. VL - 34 IS - 2 N2 - Interferon-gamma and lipopolysaccharide (IFN-gamma/LPS) induce expression of inducible nitric oxide synthase (iNOS) protein both in cells in vitro and in the brain in vivo. In cultured cells, excessive production of nitric oxide (NO) induces neuronal cell death. However, it is still unclear whether IFN-gamma and LPS might induce neuronal cell death in vivo. In this study, we examined the neuronal cell death and induction of major histocompatibility complex (MHC) antigens after microinjection of IFN-gamma/LPS into the rat hippocampus. Although microglia appeared morphologically ramified in the normal and vehicle-injected hippocampus, microinjection of IFN-gamma/LPS immediately induced the ameboid type. From days 1-7, iNOS was expressed in ameboid microglia surrounding the site of the microinjection. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells appeared among the granular neurons of the dentate gyrus on day 3 and peaked about 7 days after microinjection. When the NOS inhibitor N(G)-nitro-L-arginine (L-NA) was intraperitoneally administered prior to the microinjection, the number of TUNEL-positive neurons decreased in a L-NA dose-dependent manner. These results suggest that IFN-gamma/LPS induces delayed neuronal apoptosis in the hippocampus in vivo, and it possibly involves excessive NO production by iNOS. Thus, this animal model may be one of neurodegenerative with extensive inflammatory activation in the hippocampus. SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/10213066/Interferon_gamma_plus_lipopolysaccharide_induction_of_delayed_neuronal_apoptosis_in_rat_hippocampus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(98)00053-9 DB - PRIME DP - Unbound Medicine ER -