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Mice with targeted disruption of neurofilament light subunit display formation of protein aggregation in motoneurons and downregulation of complement receptor type 3 alpha subunit in microglia in the spinal cord at their earlier age: a possible feature in pre-clinical development of neurodegenerative diseases.

Abstract

The pathogenesis of neurodegenerative diseases prior to the onset of symptoms is generally not clear. The present study has employed a mouse model with a lack of the low-molecular-weight neurofilament subunit (NFL-/-), in which formation of protein aggregates occurs in neurons, to investigate glial cellular reactions in the lumbar cord segments of NFL-/- mice at ages from 1 to 6 months. Age-matched C57BL/6 mice serve as the control. Apparent neurofilament positive aggregates in the cytoplasm of motoneurons have been observed in NFL-/- mice. However, there were no noticeable changes in microglial numbers and GFAP staining of astrocytes. Unexpectedly, a downregulation in expression of complement receptor type 3 alpha subunit (CD11b) was detected in the spinal cord of NFL-/- mice, while there was no obvious difference between NFL-/- and C57BL/6 mice in the CD11b staining intensity of macrophages from livers and spleens. In addition, retardation in morphological transformation from activated to amoeboid microglia in response to sciatic nerve injury, differential expressions of some cytokines in the lumbar cord segments and induction of Iba-1 (ionized calcium-binding adaptor molecule-1) expression in microglia were observed in NFL-/- mice. Our results suggest not only the existence of an inhibitory niche for CD11b expression in microglia in the lumbar cord segments of NFL-/- mice but also differential microglial reactions between earlier and later stages of neuropathogenesis. Although the real cause for such inhibition is still unknown, this effect might play a particular role in the survival of the abnormal protein aggregate-bearing motoneurons in the early development stage of neurodegeneration in the NFL-/- mice.

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  • Authors+Show Affiliations

    ,

    Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore 117597, Singapore.

    , , , ,

    Source

    Brain research 1113:1 2006 Oct 03 pg 200-9

    MeSH

    Age Factors
    Animals
    Animals, Newborn
    CD11b Antigen
    Down-Regulation
    Glial Fibrillary Acidic Protein
    Immunohistochemistry
    Mice
    Mice, Inbred C57BL
    Mice, Knockout
    Microglia
    Microscopy, Electron, Transmission
    Motor Neurons
    Neurofilament Proteins
    RNA, Messenger
    Reverse Transcriptase Polymerase Chain Reaction
    Sciatic Neuropathy
    Spinal Cord

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    16920084

    Citation

    Li, Zhao Hui, et al. "Mice With Targeted Disruption of Neurofilament Light Subunit Display Formation of Protein Aggregation in Motoneurons and Downregulation of Complement Receptor Type 3 Alpha Subunit in Microglia in the Spinal Cord at Their Earlier Age: a Possible Feature in Pre-clinical Development of Neurodegenerative Diseases." Brain Research, vol. 1113, no. 1, 2006, pp. 200-9.
    Li ZH, Lu J, Tay SS, et al. Mice with targeted disruption of neurofilament light subunit display formation of protein aggregation in motoneurons and downregulation of complement receptor type 3 alpha subunit in microglia in the spinal cord at their earlier age: a possible feature in pre-clinical development of neurodegenerative diseases. Brain Res. 2006;1113(1):200-9.
    Li, Z. H., Lu, J., Tay, S. S., Wu, Y. J., Strong, M. J., & He, B. P. (2006). Mice with targeted disruption of neurofilament light subunit display formation of protein aggregation in motoneurons and downregulation of complement receptor type 3 alpha subunit in microglia in the spinal cord at their earlier age: a possible feature in pre-clinical development of neurodegenerative diseases. Brain Research, 1113(1), pp. 200-9.
    Li ZH, et al. Mice With Targeted Disruption of Neurofilament Light Subunit Display Formation of Protein Aggregation in Motoneurons and Downregulation of Complement Receptor Type 3 Alpha Subunit in Microglia in the Spinal Cord at Their Earlier Age: a Possible Feature in Pre-clinical Development of Neurodegenerative Diseases. Brain Res. 2006 Oct 3;1113(1):200-9. PubMed PMID: 16920084.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Mice with targeted disruption of neurofilament light subunit display formation of protein aggregation in motoneurons and downregulation of complement receptor type 3 alpha subunit in microglia in the spinal cord at their earlier age: a possible feature in pre-clinical development of neurodegenerative diseases. AU - Li,Zhao Hui, AU - Lu,Jia, AU - Tay,Samuel Sam Wah, AU - Wu,Ya Jun, AU - Strong,Michael Joseph, AU - He,Bei Ping, Y1 - 2006/08/22/ PY - 2006/05/10/received PY - 2006/07/08/revised PY - 2006/07/11/accepted PY - 2006/8/22/pubmed PY - 2006/12/14/medline PY - 2006/8/22/entrez SP - 200 EP - 9 JF - Brain research JO - Brain Res. VL - 1113 IS - 1 N2 - The pathogenesis of neurodegenerative diseases prior to the onset of symptoms is generally not clear. The present study has employed a mouse model with a lack of the low-molecular-weight neurofilament subunit (NFL-/-), in which formation of protein aggregates occurs in neurons, to investigate glial cellular reactions in the lumbar cord segments of NFL-/- mice at ages from 1 to 6 months. Age-matched C57BL/6 mice serve as the control. Apparent neurofilament positive aggregates in the cytoplasm of motoneurons have been observed in NFL-/- mice. However, there were no noticeable changes in microglial numbers and GFAP staining of astrocytes. Unexpectedly, a downregulation in expression of complement receptor type 3 alpha subunit (CD11b) was detected in the spinal cord of NFL-/- mice, while there was no obvious difference between NFL-/- and C57BL/6 mice in the CD11b staining intensity of macrophages from livers and spleens. In addition, retardation in morphological transformation from activated to amoeboid microglia in response to sciatic nerve injury, differential expressions of some cytokines in the lumbar cord segments and induction of Iba-1 (ionized calcium-binding adaptor molecule-1) expression in microglia were observed in NFL-/- mice. Our results suggest not only the existence of an inhibitory niche for CD11b expression in microglia in the lumbar cord segments of NFL-/- mice but also differential microglial reactions between earlier and later stages of neuropathogenesis. Although the real cause for such inhibition is still unknown, this effect might play a particular role in the survival of the abnormal protein aggregate-bearing motoneurons in the early development stage of neurodegeneration in the NFL-/- mice. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/16920084/Mice_with_targeted_disruption_of_neurofilament_light_subunit_display_formation_of_protein_aggregation_in_motoneurons_and_downregulation_of_complement_receptor_type_3_alpha_subunit_in_microglia_in_the_spinal_cord_at_their_earlier_age:_a_possible_feature_in_pre_clinical_development_of_neurodegenerative_diseases_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(06)02130-5 DB - PRIME DP - Unbound Medicine ER -