Alterations in cerebellar germinal cell division induced by graft-versus-host disease
Journal Article
·
· J. Comp. Neurol.; (United States)
A systemic immunological syndrome, graft-versus-host disease (GVHD), which does not cause inflammation or cell death in the cerebellum, is shown to retard granule cell production by decreasing the rate of DNA synthesis (S phase) and prolonging mitosis (M), at metaphase. The rate of cell production in diseased animals at postnatal day 14, quantitated by analysis of the rate of labeling of DNA with 3H-thymidine (3H-Tdr), revealed decreased ability to synthesize new DNA. The number of cells taking up 3H-Tdr label per mm2, as detected by autoradiography, was similar in 14-day-old GVHD and control tissue as was the area of the germinal matrix zone and the number of mitotically active germinal cells per mm2 in sagittal sections near the midline. However, because the total volume of the cerebellum was less, the total number of mitotically active cells in the whole cerebellum of 11-, 14-, and 17-day-old diseased animals was less than in littermate controls. Furthermore, DNA synthesis per mitotically active germinal cell was less in diseased animals at each age examined. The mitotic index was unaffected until late in the disease (day 17), suggesting that a prolongation of the cell cycle was responsible for this GVHD-induced decrease in DNA synthesis. Consistent with a prolongation of the cell cycle was the finding that the mitotic figures in 14-day-old GVHD cerebella were mostly metaphase figures, whereas those in control cerebella were, as predicted, mostly prophase. Prolongation of the cerebellar cell cycle in 11- and 14-day-old diseased animals may explain the dramatic decrease in the mitotic index, the thickness of the germinal matrix zone, and the number of germinal cells at postnatal day 17.
- Research Organization:
- Department of Cell Biology, The University of Texas Health Science Center at Dallas
- OSTI ID:
- 5343986
- Journal Information:
- J. Comp. Neurol.; (United States), Journal Name: J. Comp. Neurol.; (United States) Vol. 203:1; ISSN JCNEA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AUTORADIOGRAPHY
AZINES
BIOSYNTHESIS
BODY
BRAIN
CELL DIVISION
CENTRAL NERVOUS SYSTEM
CEREBELLUM
DNA
GERM CELLS
GRAFT-HOST REACTION
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
NEONATES
NERVOUS SYSTEM
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RIBOSIDES
SYNTHESIS
THYMIDINE
TRITIUM COMPOUNDS
UPTAKE
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AUTORADIOGRAPHY
AZINES
BIOSYNTHESIS
BODY
BRAIN
CELL DIVISION
CENTRAL NERVOUS SYSTEM
CEREBELLUM
DNA
GERM CELLS
GRAFT-HOST REACTION
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
NEONATES
NERVOUS SYSTEM
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RIBOSIDES
SYNTHESIS
THYMIDINE
TRITIUM COMPOUNDS
UPTAKE