scholarly journals Prenatal treatment with metronidazole induces cerebellar folia alteration in guinea pig fetuses

2020 ◽  
Vol 72 (4) ◽  
pp. 473-482
Author(s):  
Ivan Capo ◽  
Ivan Milenkovic ◽  
Natasa Capo ◽  
Nebojsa Stilinovic ◽  
Sasa Vukmirovic ◽  
...  
Keyword(s):  
Animal Studies ◽  
Granular Layer ◽  
Molecular Layer ◽  
Sensitive Period ◽  
Insufficient Data ◽  
Prenatal Treatment ◽  
External Granular Layer ◽  
Areal Fraction ◽  
Experimental Group ◽  
Partial Atrophy

The most sensitive period in brain development is during prenatal life. The use of antibiotics in pregnancy is still controversial. Recent studies revealed the high neurotoxic potential of the antibiotic and antiprotozoal medication, metronidazole. However, there are insufficient data from animal studies about prenatal treatment effects. We investigated the effect of prenatal treatment with metronidazole on cerebellar development in guinea pigs. Treatment with metronidazole was performed from the 42nd to the 49th day of gestation. On the 50th day of pregnancy, all dams were killed, and the cerebella of the fetuses were analyzed. Gross cerebellar changes characterized by malposition of the folia with partial atrophy were found in 12 of 19 fetuses in the experimental group, but in none of 20 control fetuses that received saline. The most affected were folia VII with depletion of the areal fraction of the external granular layer, molecular layer and the internal granular layer. Purkinje cells displayed cell distortion with loss of normal dendritic polarity. The investigation revealed cell depletion, with a disturbance of the cytoarchitectonic of the cerebellar cortex and folia alteration.

A new approach to the development of the cerebellum provided by the quail-chick marker system

Development ◽  
1990 ◽  
Vol 108 (1) ◽  
pp. 19-31 ◽  
Author(s):  
M.E. Hallonet ◽  
M.A. Teillet ◽  
N.M. Le Douarin
Keyword(s):  
Granular Layer ◽  
Sagittal Plane ◽  
Molecular Layer ◽  
Purkinje Neurons ◽  
Small Cells ◽  
Cell Type ◽  
External Granular Layer ◽  
Morphogenetic Movements ◽  
Cellular Marker ◽  
Cerebellar Cells

We have used the quail-chick chimera system to reveal the cell migrations and settling pattern involved in the construction of the cerebellum. Three types of orthotopic transplantations were carried out, between quail and chick embryos, at the 12-somite stage: exchanges of (i) the whole metencephalic vesicle, (ii) the lateral half of this vesicle and (iii) the diencephalic plus the mesencephalic vesicles. Histological study of chimeric embryos and young chicks provided the following results: longitudinal morphogenetic movements distort the embryonic neural tube as early as the fifth embryonic day, so that the dorsal limit of the mes-, met- and myelencephalic vesicles are displaced caudad and their ventral limits rostrad. This leads to a participation of mesencephalic vesicular material in the construction of the cerebellum. Cells originating in the mesencephalic vesicle are found in a rostromedial V-shaped region, in all the cerebellar cellular layers, except the external granular layer, the presumptive territory of which is entirely located in the metencephalic vesicle. The chimerism of the rostromedial part of the cerebellum allows the analysis of the origin of the various cerebellar cell types. We find (i) that the Purkinje cells always have the same cellular marker as the ventricular epithelium radially beneath them. This strongly suggests that these cells reach their final localization following strictly radial migrations. (ii) Most of the small cells surrounding the Purkinje neurons and most of the neurons and glial cells of the molecular layer are also of the same type as the ventricular epithelium they surmount, i.e. different from the type of the external granular layer cells. Therefore, they are not derived from the external granular layer and are not of the same origin as the granule cells as previously believed. Unilateral substitutions of the metencephalic vesicle revealed that transverse cell migrations occur across the sagittal plane. They have been observed mainly in the inner and external granular layers, but also, though to a lesser extent, in the molecular layer and in the cell layer located at the level of the Purkinje neurons. These observations show that the position of cerebellar cells is determined by both morphogenetic movements and cell type-specific active radial and tangential migrations. The quail-chick chimera system is thus able to provide new information both on the origin of cerebellar cells and how each cell type assumes its final position.

scholarly journals Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum

2000 ◽  
Vol 14 (8) ◽  
pp. 994-1004 ◽  
Author(s):  
Silvia Marino ◽  
Marc Vooijs ◽  
Hanneke van der Gulden ◽  
Jos Jonkers ◽  
Anton Berns
Keyword(s):  
Tumor Suppressor Genes ◽  
Granular Layer ◽  
Molecular Layer ◽  
Precursor Cells ◽  
Loss Of Function ◽  
External Granular Layer ◽  
Embryonal Tumors ◽  
Mortality And Morbidity ◽  
Null Mutant Mice ◽  
Developing Cerebellum

Medulloblastomas are among the most common malignancies in childhood, and they are associated with substantial mortality and morbidity. The molecular pathogenesis as well as the ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre–LoxP-mediated inactivation ofRb and p53 tumor suppressor genes in the cerebellar external granular layer (EGL) cells. GFAP–Cre-mediated recombination was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum.GFAP–Cre;RbLoxP/LoxP;p53−/−or LoxP/LoxP mice developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. Our results demonstrate that loss of function of RB is essential for medulloblastoma development in the mouse and strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL.

scholarly journals Sequential expression and differential function of multiple adhesion molecules during the formation of cerebellar cortical layers.

1987 ◽  
Vol 104 (2) ◽  
pp. 331-342 ◽  
Author(s):  
C M Chuong ◽  
K L Crossin ◽  
G M Edelman
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Granule Cell ◽  
Cell Adhesion Molecule ◽  
Granular Layer ◽  
Molecular Layer ◽  
External Granular Layer ◽  
Cortical Layers

We have correlated the times of appearance of the neural cell adhesion molecule (N-CAM), the neuron-glia cell adhesion molecule (Ng-CAM), and the extracellular matrix protein, cytotactin, during the development of the chicken cerebellar cortex, and have shown that these molecules make different functional contributions to granule cell migration. Immunofluorescent staining showed distinct spatiotemporal expression sequences for each adhesion molecule. N-CAM was present at all times in all layers. However, the large cytoplasmic domain polypeptide of N-CAM was always absent from the external granular layer and was enriched in the molecular layer as development proceeded. Ng-CAM began to be expressed in the premigratory granule cells just before migration and later disappeared from cell bodies but remained on parallel fibers. Cytotactin, which is synthesized by glia and not by neurons, appeared first in a speckled pattern within the external granular layer and later appeared in a continuous pattern along the Bergmann glia; it was also enriched in the molecular layer. After we established their order of appearance, we tested the separate functions of these adhesion molecules in granule cell migration by adding specific antibodies against each molecule to cerebellar explant cultures that had been labeled with tritiated thymidine and then measuring the differential distribution of labeled cells in the forming layers. Anti-N-CAM showed marginal effects. In contrast, anti-Ng-CAM arrested most cells in the external granular layer, while anti-cytotactin arrested most cells in the molecular layer. Time course analyses combined with sequential addition of different antibodies in different orders showed that anti-Ng-CAM had a major effect in the early period (first 36 h in culture) and a lesser effect in the second part of the culture period, while anti-cytotactin had essentially no effect at the earlier time but had major effects at a later period (18-72 h in culture). The two major stages of cerebellar granule cell migration thus appear to be differentially affected by distinct adhesion molecules of different cellular origins, binding mechanisms, and overall distributions. The results indicated that local cell surface modulation of adhesion molecules of different specificities at defined stages and sites is essential to the formation of cerebellar cortical layers.

scholarly journals QUANTITATIVE ANALYSIS OF CELL PROLIFERATION AND DIFFERENTIATION IN THE CORTEX OF THE POSTNATAL MOUSE CEREBELLUM

1967 ◽  
Vol 32 (2) ◽  
pp. 277-287 ◽  
Author(s):  
Setsuya Fujita
Keyword(s):  
Granular Layer ◽  
Molecular Layer ◽  
External Granular Layer ◽  
Proliferating Cells ◽  
Daily Production ◽  
Cell Proliferation And Differentiation ◽  
Matrix Cell ◽  
Proliferation And Differentiation ◽  
Before And After ◽  
Mantle Layer

The generation cycle of germinative cells (external matrix cells) in the external granular layer of the cerebellar cortex of the 10-to 11-day-old mouse was studied by radioautography following repeated injections of H3-thymidine. The generation time is 19 hr, presynthetic time 8.5 hr, DNA-synthetic time 8 hr, postsynthetic time 2 hr, and mitotic time 0.5 hr. These proliferating cells occupy the outer half of the external granular layer and make up the external matrix layer. Neuroblasts are differentiated from the external matrix cell, migrate out from the layer and accumulate in the inner half of the external granular layer to form the external mantle layer. The transit time of the neuroblasts in the external mantle layer is 28 hr. Thereafter, they migrate farther into the molecular layer and the internal granular layer. By means of long-term cumulative labeling, the rate of daily production of neuroblasts from the external matrix cell is studied in quantitative terms. It becomes clear that the entire population of the inner granule neurons arises postnatally in the external granular layer between 1 and 18 days of age and that 95% of them is produced between postnatal days 4 and 15. Finally, the fate of the cells in the external granular layer at its terminal stage was studied by marking the cells with H3-thymidine during 15–16 days of life and following their subsequent migration and developmental changes up to 21 days of life. Comparison of radioautographs taken before and after the migration disclosed that the external matrix cells give rise to a small number of neuroglia cells. This finding revealed their multipotential nature.

Effect of Reserpine on the Differentiation of the External Granular Layer of the Cerebellum in the Chick Embryo

1987 ◽  
Vol 129 (4) ◽  
pp. 265-269 ◽  
Author(s):  
A. Espinar ◽  
A. Quesada ◽  
M. Martinez-de-la-Torre ◽  
J.A. Armengol
Keyword(s):  
Chick Embryo ◽  
Granular Layer ◽  
External Granular Layer

scholarly journals The Effectiveness of Group Training of CBT-Based Stress Management on Anxiety, Psychological Hardiness and General Self-Efficacy Among University Students

2015 ◽  
Vol 8 (6) ◽  
pp. 47 ◽  
Author(s):  
Hamdam Molla Jafar ◽  
Seddigheh Salabifard ◽  
Seyedeh Maryam Mousavi ◽  
Zahra Sobhani
Keyword(s):  
University Students ◽  
Stress Management ◽  
Self Efficacy ◽  
Management Training ◽  
Sensitive Period ◽  
Control Group ◽  
Stress Management Training ◽  
Psychological Hardiness ◽  
General Self Efficacy ◽  
Experimental Group

<p><strong>BACKGROUND: </strong>Admission to university is a very sensitive period of life for efficient, active, and young workforces in any country, and it is mostly associated with many changes in social and human relationships. These changes lead to anxiety in students. Moreover, humans need certain functions in order to adaptively deal with different life situations and challenges. By training stress management, these functions can help human acquire the required abilities.</p> <p><strong>OBJECTIVE:</strong> The present study was aimed at investigating the effectiveness of stress management training in anxiety, psychological hardiness, and general self-efficacy among university students.</p> <p><strong>METHOD:</strong> The study was a quasi-experimental intervention (pretest-posttest-follow-up) including a control group, it was a fundamental applied study. The statistical population consisted of all students of Islamic Azad University, Karaj, Iran. Convenient sampling was employed to select 30 students who were divided into an experimental group (n=15) and a control group (n=15). Before stress management training, both groups filled out Beck Anxiety Inventory, Long and Goulet scale of psychological hardiness, and General Self-efficacy Scale (GSE-10). Afterwards, the experimental group was provided with stress management training. And after the experiment, the abovementioned questionnaires and scales were responded by the two groups. Finally the collected data were analyzed and compared using one-way MANOVA.</p> <p><strong>RESULTS:</strong> The results of MANOVA indicated that there was a significant difference between the two groups in terms of anxiety, hardiness, and general self-efficacy (p&lt;0.001).</p> <p><strong>CONCLUSION:</strong> According to the results of the present study and those of previous investigations that are in agreement with those of the present study, it can be concluded that stress management among university students cause anxiety to drop; moreover, it enhances their psychological hardiness and self-efficacy. In regard with the role and importance of stress management, training this skill should be included in educational plans of university.</p>

scholarly journals Kola nut from Cola nitida vent. Schott administered to pregnant rats induces histological alterations in pups’ cerebellum

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247573
Author(s):  
Foluso A. Atiba ◽  
Amos A. Fatokun ◽  
Innocent O. Imosemi ◽  
Adefolarin O. Malomo
Keyword(s):  
Human Brain ◽  
Granular Layer ◽  
Molecular Layer ◽  
B Cell Lymphoma ◽  
First Trimester ◽  
Cresyl Violet ◽  
Pregnant Rats ◽  
Over Expression ◽  
Initial Reduction ◽  
Cola Nitida

Kola nut (from Cola nitida) is popular in Nigeria and West Africa and is commonly consumed by pregnant women during the first trimester to alleviate morning sickness and dizziness. There is, however, a dearth of information on its effects on the developing brain. This study, therefore, investigated the potential effects of kola nut on the structure of the developing neonatal and juvenile cerebellum in the rat. Pregnant Wistar rats were administered water (as control) or crude (aqueous) kola nut extract at 400, 600, and 800 mg/kg body weight orally, from pregnancy to day 21 after birth. On postnatal days 1, 7, 14, 21 and 28, the pups were weighed, anaesthetised, sacrificed and perfused with neutral buffered formalin. Their brains were dissected out, weighed and the cerebellum preserved in 10% buffered formalin. Paraffin sections of the cerebellum were stained with haematoxylin and eosin for cerebellar cytoarchitecture, cresyl violet stain for Purkinje cell count, Glial Fibrillary Acidic Protein (GFAP) immunohistochemistry (IHC) for estimation of gliosis, and B-cell lymphoma 2 (Bcl-2) IHC for apoptosis induction. The kola nut-treated rats exhibited initial reduction in body and brain weights, persistent external granular layer, increased molecular layer thickness, and loss of Bergmann glia. Their Purkinje cells showed reduction in density, loss of dendrites and multiple layering, and their white matter showed neurodegeneration (spongiosis) and GFAP and Bcl-2 over-expression, with evidence of reactive astrogliosis. This study, therefore, demonstrates that kola nut, administered repeatedly at certain doses to pregnant dams, could disrupt normal postnatal cerebellar development in their pups. The findings suggest potential deleterious effects of excessive kola nut consumption on human brain and thus warrant further studies to understand the wider implications for human brain development.

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