scholarly journals Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia

2018 ◽  
Vol 306 ◽  
pp. 209-221 ◽  
Author(s):  
Igor Y. Iskusnykh ◽  
Randal K. Buddington ◽  
Victor V. Chizhikov
Keyword(s):  
Cell Proliferation ◽  
Preterm Birth ◽  
Granule Cell ◽  
Bergmann Glia ◽  
Cerebellar Development

scholarly journals Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs

2020 ◽  
Vol 10 (8) ◽  
pp. 475 ◽  
Author(s):  
Daniel Chizhikov ◽  
Randal K. Buddington ◽  
Igor Y. Iskusnykh
Keyword(s):  
Preterm Birth ◽  
Docosahexaenoic Acid ◽  
Purkinje Cells ◽  
Cognitive Processing ◽  
Granule Cell ◽  
Granule Cells ◽  
Cell Layer ◽  
Granule Cell Layer ◽  
Cerebellar Development ◽  
Control Group

Preterm birth, a major contributor to infant mortality and morbidity, impairs development of the cerebellum, the brain region involved in cognitive processing and motor function. Previously, we showed that at term-equivalent age, preterm pigs that received formula supplemented with docosahexaenoic acid (DHA) esterified to phosphatidylserine (PS) had cerebellar weights similar to those of newborn term pigs and were heavier than control preterm pigs. However, whether PS-DHA promotes the development of specific cerebellar cell populations or enhances key developmental processes remains unknown. Here we investigated the effects of the PS-DHA on development of the cerebellum in preterm pigs delivered via caesarean section and reared for ten days on a milk replacer with either PS-DHA (experimental group) or sunflower oil (control group). Upon necropsy, key cerebellar populations were analyzed using immunohistochemistry. Consumption of PS-DHA was associated with the expansion of undifferentiated granule cell precursors and increased proliferation in the external granule cell layer (EGL). Preterm pigs that received PS-DHA also had significantly fewer apoptotic cells in the internal granule cell layer (IGL) that contains differentiated granule neurons. PS-DHA did not affect the number of differentiating granule cells in the inner EGL, thickness of the inner EGL, density of Purkinje cells, or Bergmann glial fibers, or diameter of Purkinje cells. Thus, PS-DHA may support cerebellar development in preterm subjects by enhancing proliferation of granule cells, a process specifically inhibited by preterm birth, and increasing the survival of granule cells in the IGL. These findings suggest that PS-DHA is a promising candidate for clinical studies directed at enhancing brain development.

scholarly journals Kruppel-Like Factor 4 Regulates Granule Cell Pax6 Expression and Cell Proliferation in Early Cerebellar Development

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0134390 ◽  
Author(s):  
Peter Zhang ◽  
Thomas Ha ◽  
Matt Larouche ◽  
Douglas Swanson ◽  
Dan Goldowitz
Keyword(s):  
Cell Proliferation ◽  
Granule Cell ◽  
Cerebellar Development ◽  
Pax6 Expression

Preterm Birth and Disruptive Cerebellar Development: Assessment of Perinatal Risk Factors

2006 ◽  
Vol 210 (S 5) ◽  
Author(s):  
A Messerschmidt ◽  
D Prayer ◽  
PC Brugger ◽  
G Zoder ◽  
W Sterniste ◽  
...  
Keyword(s):  
Risk Factors ◽  
Preterm Birth ◽  
Cerebellar Development ◽  
Perinatal Risk Factors ◽  
Perinatal Risk ◽  
Development Assessment

scholarly journals Cell Proliferation and Granule Cell Dispersion in Human Hippocampal Sclerosis

2005 ◽  
Vol 64 (3) ◽  
pp. 194-201 ◽  
Author(s):  
Maria Thom ◽  
Lillian Martinian ◽  
Gareth Williams ◽  
Kai Stoeber ◽  
Sanjay M. Sisodiya
Keyword(s):  
Cell Proliferation ◽  
Granule Cell ◽  
Hippocampal Sclerosis ◽  
Cell Dispersion

Role of Pax6 in development of the cerebellar system

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3585-3596 ◽  
Author(s):  
D. Engelkamp ◽  
P. Rashbass ◽  
A. Seawright ◽  
V. van Heyningen
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Long Distance ◽  
Cerebellar Granule ◽  
Precerebellar Nuclei ◽  
Rhombic Lip

Post-mitotic neurons generated at the rhombic lip undertake long distance migration to widely dispersed destinations, giving rise to cerebellar granule cells and the precerebellar nuclei. Here we show that Pax6, a key regulator in CNS and eye development, is strongly expressed in rhombic lip and in cells migrating away from it. Development of some structures derived from these cells is severely affected in Pax6-null Small eye (Pax6(Sey)/Pax6(Sey)) embryos. Cell proliferation and initial differentiation seem unaffected, but cell migration and neurite extension are disrupted in mutant embryos. Three of the five precerebellar nuclei fail to form correctly. In the cerebellum the pre-migratory granule cell sub-layer and fissures are absent. Some granule cells are found in ectopic positions in the inferior colliculus which may result from the complete absence of Unc5h3 expression in Pax6(Sey)/Pax6(Sey) granule cells. Our results suggest that Pax6 plays a strong role during hindbrain migration processes and at least part of its activity is mediated through regulation of the netrin receptor Unc5h3.

scholarly journals Preterm Birth Impedes Structural and Functional Development of Cerebellar Purkinje Cells in the Developing Baboon Cerebellum

2020 ◽  
Vol 10 (12) ◽  
pp. 897
Author(s):  
Tara Barron ◽  
Jun Hee Kim
Keyword(s):  
Preterm Birth ◽  
Action Potential ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Late Gestation ◽  
Cerebellar Development ◽  
Layer Width ◽  
Action Potential Waveform ◽  
Developmental Features ◽  
Potential Waveform

Human cerebellar development occurs late in gestation and is hindered by preterm birth. The fetal development of Purkinje cells, the primary output cells of the cerebellar cortex, is crucial for the structure and function of the cerebellum. However, morphological and electrophysiological features in Purkinje cells at different gestational ages, and the effects of neonatal intensive care unit (NICU) experience on cerebellar development are unexplored. Utilizing the non-human primate baboon cerebellum, we investigated Purkinje cell development during the last trimester of pregnancy and the effect of NICU experience following premature birth on developmental features of Purkinje cells. Immunostaining and whole-cell patch clamp recordings of Purkinje cells in the baboon cerebellum at different gestational ages revealed that molecular layer width, driven by Purkinje dendrite extension, drastically increased and refinement of action potential waveform properties occurred throughout the last trimester of pregnancy. Preterm birth followed by NICU experience for 2 weeks impeded development of Purkinje cells, including action potential waveform properties, synaptic input, and dendrite extension compared with age-matched controls. In addition, these alterations impact Purkinje cell output, reducing the spontaneous firing frequency in deep cerebellar nucleus (DCN) neurons. Taken together, the primate cerebellum undergoes developmental refinements during late gestation, and NICU experience following extreme preterm birth influences morphological and physiological features in the cerebellum that can lead to functional deficits.

Close homologue of adhesion molecule L1 promotes survival of Purkinje and granule cells and granule cell migration during murine cerebellar development

2009 ◽  
Vol 513 (5) ◽  
pp. 496-510 ◽  
Author(s):  
Igor Jakovcevski ◽  
Janina Siering ◽  
Gunnar Hargus ◽  
Nicole Karl ◽  
Laura Hoelters ◽  
...  
Keyword(s):  
Cell Migration ◽  
Adhesion Molecule ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Development ◽  
Close Homologue

scholarly journals Deficits in Motor Coordination with Aberrant Cerebellar Development in Mice Lacking Testicular Orphan Nuclear Receptor 4

2005 ◽  
Vol 25 (7) ◽  
pp. 2722-2732 ◽  
Author(s):  
Yei-Tsung Chen ◽  
Loretta L. Collins ◽  
Hideo Uno ◽  
Chawnshang Chang
Keyword(s):  
Nuclear Receptor ◽  
Granule Cell ◽  
Motor Coordination ◽  
Granule Cells ◽  
Molecular Layer ◽  
Granule Cell Layer ◽  
Abnormal Development ◽  
Cerebellar Development ◽  
Morphological Development ◽  
Orphan Nuclear Receptor

ABSTRACT Since testicular orphan nuclear receptor 4 (TR4) was cloned, its physiological function has remained largely unknown. Throughout postnatal development, TR4-knockout (TR4−/−) mice exhibited behavioral deficits in motor coordination, suggesting impaired cerebellar function. Histological examination of the postnatal TR4−/− cerebellum revealed gross abnormalities in foliation; specifically, lobule VII in the anterior vermis was missing. Further analyses demonstrated that the laminations of the TR4−/− cerebellar cortex were changed, including reductions in the thickness of the molecular layer and the internal granule layer, as well as delayed disappearance of the external granule cell layer (EGL). These lamination irregularities may result from interference with granule cell proliferation within the EGL, delayed inward migration of postmitotic granule cells, and a higher incidence of apoptotis. In addition, abnormal development of Purkinje cells was observed in the postnatal TR4−/− cerebellum, as evidenced by aberrant dendritic arborization and reduced calbindin staining intensity. Expression of Pax-6, Sonic Hedgehog (Shh), astrotactin (Astn), reelin, and Cdk-5, genes correlated with the morphological development of the cerebellum, is reduced in the developing TR4−/− cerebellum. Together, our findings suggest that TR4 is required for normal cerebellar development.

scholarly journals Cerebellar granule cells contain a membrane mitogen for cultured Schwann cells.

1989 ◽  
Vol 108 (2) ◽  
pp. 607-611 ◽  
Author(s):  
P W Mason ◽  
J W Bigbee ◽  
G H DeVries
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Cultures ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Proteoglycan Synthesis ◽  
Cerebellar Granule ◽  
Mitogenic Signal

Proliferation of Schwann cells is one of the first events that occurs after contact with a growing axon. To further define the distribution and properties of this axonal mitogen, we have (a) cocultured cerebellar granule cells, which lack glial ensheathment in vivo with Schwann cells; and (b) exposed Schwann cell cultures to isolated granule cell membranes. Schwann cells cocultured with granule cells had a 30-fold increase in the labeling index over Schwann cells cultured alone, suggesting that the mitogen is located on the granule cell surface. Inhibition of granule cell proteoglycan synthesis caused a decrease in the granule cells' ability to stimulate Schwann cell proliferation. Membranes isolated from cerebellar granule cells when added to Schwann cell cultures caused a 45-fold stimulation in [3H]thymidine incorporation. The granule cell mitogenic signal was heat and trypsin sensitive and did not require lysosomal processing by Schwann cells to elicit its proliferative effect. The ability of granule cells and their isolated membranes to stimulate Schwann cell proliferation suggests that the mitogenic signal for Schwann cells is a ubiquitous factor present on all axons regardless of their ultimate state of glial ensheathment.

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