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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.
Brain Res 2006; 1113(1):200-9BR

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.

Authors+Show Affiliations

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore 117597, Singapore.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -