Reactive gliosis of immature Bergmann glia and microglial cell activation in response to cell death of granule cell precursors induced by methylazoxymethanol treatment in developing rat cerebellum. 1998

M Lafarga, and M A Andres, and E Calle, and M T Berciano
Departamento de Anatomía y Biología Celular, Facultad de Medicina, Santander, Spain. lafargam@medi-unican.es

The morphology, organization and expression of proliferating cell nuclear antigen (PCNA) and the cytoskeletal proteins vimentin and GFAP in immature Bergmann glial cells were studied after a developmental injury induced by a single dose of the cytotoxic agent methylazoxymethanol (MAM) administered on postnatal day 5. This drug, which produces cell death of cerebellar granule cell precursors, did not induce apoptosis in Bergmann glial cells, which are in a proliferative stage. After MAM treatment, PCNA staining showed a severe depletion of PCNA-positive granule cell precursors, whereas PCNA-positive Bergmann glial nuclei in the Purkinje cell layer were preserved. Moreover, the quantitative analysis revealed an increase in the density of both Purkinje cells and PCNA-positive Bergmann glial cells per mm of Purkinje cell layer in MAM-treated rats relative to age-matched controls, but the numerical ratio between these two cell populations remains invariable after MAM treatment. Vimentin and GFAP immunocytochemistry revealed a reinforcement of the Bergmann glial palisade with overexpression of both proteins and thicker immunoreactive glial processes in MAM-treated rats. At the ultrastructural level, Bergmann glial processes closely associated with dying cells in different stages of apoptosis were observed. Frequently, these processes enclosed dying cells in extracellular compartments. Furthermore, phagosomes containing apoptotic bodies were found in Bergmann fibers of MAM-treated rats. These data indicate that the cell death of granule cell precursors triggers a reactive response in immature Bergmann glia. We suggest that this response reflects the plasticity of Bergmann glia to control the neuronal microenvironment in the maturing molecular layer, protecting healthy cells against the potentially harmful contents of dying cells. In situ labeling of cell death with the TUNEL method revealed that the cell death of granule cell precursors is of the apoptotic type. The participation of ameboid microglial cells in the phagocytosis of apoptotic cells was shown with tomato lectin histochemistry and ultrastructural analysis. Moreover, the presence of mitosis in this microglial population demonstrates its proliferative activity in regions of extensive cell death.

UI MeSH Term Description Entries
D008297 Male Males
D008746 Methylazoxymethanol Acetate The aglycone of CYCASIN. It acts as a potent carcinogen and neurotoxin and inhibits hepatic DNA, RNA, and protein synthesis. (Methyl-ONN-azoxy)methanol Acetate,Acetate, Methylazoxymethanol
D008938 Mitosis A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species. M Phase, Mitotic,Mitotic M Phase,M Phases, Mitotic,Mitoses,Mitotic M Phases,Phase, Mitotic M,Phases, Mitotic M
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D002525 Cerebellar Cortex The superficial GRAY MATTER of the CEREBELLUM. It consists of two main layers, the stratum moleculare and the stratum granulosum. Cortex Cerebelli,Cerebelli, Cortex,Cerebellus, Cortex,Cortex Cerebellus,Cortex, Cerebellar
D005904 Glial Fibrillary Acidic Protein An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000. Glial Intermediate Filament Protein,Astroprotein,GFA-Protein,Glial Fibrillary Acid Protein,GFA Protein
D005911 Gliosis The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. Astrocytosis,Astrogliosis,Glial Scar,Astrocytoses,Glial Scars,Scar, Glial
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013234 Stem Cells Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells. Colony-Forming Units,Mother Cells,Progenitor Cells,Colony-Forming Unit,Cell, Mother,Cell, Progenitor,Cell, Stem,Cells, Mother,Cells, Progenitor,Cells, Stem,Colony Forming Unit,Colony Forming Units,Mother Cell,Progenitor Cell,Stem Cell
D014746 Vimentin An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000.

Related Publications

M Lafarga, and M A Andres, and E Calle, and M T Berciano
October 1977, Anatomy and embryology,
M Lafarga, and M A Andres, and E Calle, and M T Berciano
April 2013, Molecular neurobiology,
M Lafarga, and M A Andres, and E Calle, and M T Berciano
January 1999, Brain research. Developmental brain research,
M Lafarga, and M A Andres, and E Calle, and M T Berciano
March 1988, Scanning microscopy,
M Lafarga, and M A Andres, and E Calle, and M T Berciano
December 2023, Scientific reports,
M Lafarga, and M A Andres, and E Calle, and M T Berciano
June 1998, Journal of chemical neuroanatomy,
M Lafarga, and M A Andres, and E Calle, and M T Berciano
January 1980, Developmental neuroscience,
M Lafarga, and M A Andres, and E Calle, and M T Berciano
August 2018, Experimental neurology,
M Lafarga, and M A Andres, and E Calle, and M T Berciano
December 2005, Brain research. Developmental brain research,
M Lafarga, and M A Andres, and E Calle, and M T Berciano
August 2018, Cerebellum (London, England),
Copied contents to your clipboard!