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Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure.

Abstract

We investigated the effect of trimethyltin (TMT), a well-known neurotoxicant, on murine hippocampal neurons and glial cells. Three days following intraperitoneal (i.p.) injection of TMT into 1-month-old Balb/c mice at a dose of 2.5 mg/kg body weight we detected damage of the dentate gyrus granular neurons. The dying cells displayed chromatin condensation and internucleosomal DNA fragmentation, which are the most characteristic features of apoptosis. To study, if prolyl oligopeptidase is engaged in neuronal apoptosis following TMT administration, we pretreated mice with the specific inhibitor--Fmoc-Pro-ProCN in doses of 5 and 10 mg/kg body weight (i.p. injection). Three days following injection we did not observe any attenuation of neurotoxic damage, regardless of inhibitor dose, indicating the lack of prolyl oligopeptidase contribution to neuronal injury caused by TMT. The neurodegeneration was associated with reactive astrogliosis in whole hippocampus, but particularly in injured dentate gyrus. The reactive astrocytes showed an increased nerve growth factor (NGF) expression in ventral as well as dorsal hippocampal parts. NGF immunoreactivity was also augmented in neurons of CA3/CA4 areas, which were almost totally spared after TMT intoxication. It suggested a role for this neurotrophin in protection of pyramidal cells from loss of connection between CA3/CA4 and dentate gyrus fields. The granule neurons' death was accompanied by increased histochemical staining with isolectin B4, a marker of microglia, in the region of neurodegeneration. The microglial cells displayed ramified and ameboid morphology, characteristic of their reactive forms. Activated microglia were the main source of interleukin 1beta (IL-1beta). It is possible that this cytokine may participate in neurodegeneration of granule cells. Alternatively, IL-1beta elaborated by microglia could play a role in increasing NGF expression, both in astroglia and in CA3/CA4 neurons.

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  • Authors+Show Affiliations

    ,

    Laboratory of Neurochemistry, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3 Street, 02-093, Warsaw, Poland.

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    Source

    Brain research 912:2 2001 Sep 07 pg 116-27

    MeSH

    Animals
    Apoptosis
    Astrocytes
    Bisbenzimidazole
    Dentate Gyrus
    Enzyme Inhibitors
    Female
    Fluorescent Dyes
    Glial Fibrillary Acidic Protein
    Gliosis
    Immunohistochemistry
    In Situ Nick-End Labeling
    Interleukin-1
    Lectins
    Mice
    Mice, Inbred BALB C
    Microglia
    Nerve Degeneration
    Nerve Growth Factor
    Neuroglia
    Neurons
    Neurotoxins
    Pyramidal Cells
    Serine Endopeptidases
    Trimethyltin Compounds

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    11532427

    Citation

    Fiedorowicz, A, et al. "Dentate Granule Neuron Apoptosis and Glia Activation in Murine Hippocampus Induced By Trimethyltin Exposure." Brain Research, vol. 912, no. 2, 2001, pp. 116-27.
    Fiedorowicz A, Figiel I, Kamińska B, et al. Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure. Brain Res. 2001;912(2):116-27.
    Fiedorowicz, A., Figiel, I., Kamińska, B., Zaremba, M., Wilk, S., & Oderfeld-Nowak, B. (2001). Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure. Brain Research, 912(2), pp. 116-27.
    Fiedorowicz A, et al. Dentate Granule Neuron Apoptosis and Glia Activation in Murine Hippocampus Induced By Trimethyltin Exposure. Brain Res. 2001 Sep 7;912(2):116-27. PubMed PMID: 11532427.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure. AU - Fiedorowicz,A, AU - Figiel,I, AU - Kamińska,B, AU - Zaremba,M, AU - Wilk,S, AU - Oderfeld-Nowak,B, PY - 2001/9/5/pubmed PY - 2002/1/5/medline PY - 2001/9/5/entrez SP - 116 EP - 27 JF - Brain research JO - Brain Res. VL - 912 IS - 2 N2 - We investigated the effect of trimethyltin (TMT), a well-known neurotoxicant, on murine hippocampal neurons and glial cells. Three days following intraperitoneal (i.p.) injection of TMT into 1-month-old Balb/c mice at a dose of 2.5 mg/kg body weight we detected damage of the dentate gyrus granular neurons. The dying cells displayed chromatin condensation and internucleosomal DNA fragmentation, which are the most characteristic features of apoptosis. To study, if prolyl oligopeptidase is engaged in neuronal apoptosis following TMT administration, we pretreated mice with the specific inhibitor--Fmoc-Pro-ProCN in doses of 5 and 10 mg/kg body weight (i.p. injection). Three days following injection we did not observe any attenuation of neurotoxic damage, regardless of inhibitor dose, indicating the lack of prolyl oligopeptidase contribution to neuronal injury caused by TMT. The neurodegeneration was associated with reactive astrogliosis in whole hippocampus, but particularly in injured dentate gyrus. The reactive astrocytes showed an increased nerve growth factor (NGF) expression in ventral as well as dorsal hippocampal parts. NGF immunoreactivity was also augmented in neurons of CA3/CA4 areas, which were almost totally spared after TMT intoxication. It suggested a role for this neurotrophin in protection of pyramidal cells from loss of connection between CA3/CA4 and dentate gyrus fields. The granule neurons' death was accompanied by increased histochemical staining with isolectin B4, a marker of microglia, in the region of neurodegeneration. The microglial cells displayed ramified and ameboid morphology, characteristic of their reactive forms. Activated microglia were the main source of interleukin 1beta (IL-1beta). It is possible that this cytokine may participate in neurodegeneration of granule cells. Alternatively, IL-1beta elaborated by microglia could play a role in increasing NGF expression, both in astroglia and in CA3/CA4 neurons. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/11532427/Dentate_granule_neuron_apoptosis_and_glia_activation_in_murine_hippocampus_induced_by_trimethyltin_exposure_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(01)02675-0 DB - PRIME DP - Unbound Medicine ER -