Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum

McDougall, Annie R A; Wiradjaja, Vanny; Azhan, Aminath; Li, Anqi; Hale, Nadia; Wlodek, Mary E.; Hooper, Stuart B.; Wallace, Megan Jane; Tolcos, Mary

doi:10.1159/000470902

Cited by 22 publications

(22 citation statements)

References 58 publications

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“…The linear density of fibres (fibres/mm) was then determined by dividing the number of fibres by length of the line. We also qualitatively assessed the morphology of Bergmann glia, for example for evidence of fibre disorganisation (tangled or irregularly orientated fibres), and disrupted fibre integrity (damaged/degenerating fibres and disconnected fibres, i.e., those that did not extend the full length from the IGL to the upper EGL) as previously described [24]. …”

Section: Methodsmentioning

confidence: 99%

“…In addition, children who were GR in utero have decreased white matter volume in the cerebellum [17] and cerebellar underdevelopment in IUGR infants is linked to altered cerebellar connectivity and function [18]. In animal models of IUGR induced via either chronic [19-23] or acute [24] placental insufficiency, we have already demonstrated that several aspects of cerebellar development are adversely affected when assessed pre- and postnatally. In GR guinea pigs induced by chronic placental insufficiency (CPI) throughout the second half of gestation [21], there are significant reductions in: the number of Purkinje cells [25], the volumes of the molecular layer (ML), internal granular layer (IGL) and white matter [19, 22, 25], and alterations in the maturation of myelin [22].…”

Section: Introductionmentioning

confidence: 99%

“…In GR guinea pigs induced by chronic placental insufficiency (CPI) throughout the second half of gestation [21], there are significant reductions in: the number of Purkinje cells [25], the volumes of the molecular layer (ML), internal granular layer (IGL) and white matter [19, 22, 25], and alterations in the maturation of myelin [22]. In IUGR rats induced via acute placental insufficiency and assessed postnatally, we have shown that, compared with controls, Bergmann glia are disorganised and reduced in density, and the width of the external granular layer (EGL) is 30% greater [24]. In GR foetal sheep induced by CPI throughout gestation [26] or at mid-gestation [23] we have demonstrated marked reductions from normal growth in the areas of the ML, IGL and white matter, and in the development of the Purkinje cell dendritic arborisation [23].…”

Section: Introductionmentioning

confidence: 99%

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Intrauterine Growth Restriction Affects Cerebellar Granule Cells in the Developing Guinea Pig Brain

et al. 2018

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Intrauterine growth restriction (IUGR) can lead to adverse neurodevelopmental sequelae in postnatal life. However, the effects of IUGR on the cerebellum are still to be fully elucidated. A major determinant of growth and development of the cerebellum is proliferation and subsequent migration of cerebellar granule cells. Our objective was to determine whether IUGR, induced by chronic placental insufficiency (CPI) in guinea pigs, results in abnormal cerebellar development due to deficits suggestive of impaired granule cell proliferation and/or migration. CPI was induced by unilateral ligation of the uterine artery at mid-gestation, producing growth-restricted (GR) foetuses at 52 and 60 days of gestation (dg), and neonates at 1 week postnatal age (term approx. 67 dg). Controls were from sham-operated animals. In GR foetuses compared with controls at 52 dg, the external granular layer (EGL) width and internal granular layer (IGL) area were similar. In GR foetuses compared with controls at 60 dg: (a) the EGL width was greater (p < 0.005); (b) the IGL area was smaller (p < 0.005); (c) the density of Ki67-negative (postmitotic) granule cells in the EGL was greater (p < 0.01); (d) the somal area of Purkinje cells was reduced (p < 0.005), and (e) the linear density of Bergmann glia was similar. The EGL width in GR foetuses at 60 dg was comparable to that of 52 dg control and GR foetuses. The pattern of p27-immunoreactivity in the EGL was the inverse of Ki67-immunoreactivity at both foetal ages; there was no difference between control and GR foetuses at either age in the width of p27-immunoreactivity, or in the percentage of the EGL width that it occupied. In the molecular layer of GR neonates compared with controls there was an increase in the areal density of granule cells (p < 0.05) and in the percentage of migrating to total number of granule cells (p < 0.01) at 1 week but not at 60 dg (p > 0.05). Thus, we found no specific evidence that IUGR affects granule cell proliferation, but it alters the normal program of migration to the IGL and, in addition, the development of Purkinje cells. Such alterations will likely affect the development of appropriate circuitry and have implications for cerebellar function.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intrauterine Growth Restriction Affects Cerebellar Granule Cells in the Developing Guinea Pig Brain

et al. 2018

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“…Besides the above-mentioned organs, Trop2 is also expressed in lungs [ 17 , 18 ], intestines [ 19 ], stomach [ 20 ], bladder [ 21 ], and kidneys [ 22 ] during embryonal and fetal development. Trop2 protein was also detected in granule cells in all layers of the developing cerebellum, particularly in postmitotic cells, suggesting its function in regulation of cell migration [ 23 ]. In the damaged adult stomach, Trop2 is re-expressed and might be associated with regeneration processes [ 20 ].…”

Section: Trop2 In Healthy Tissue and Developmentmentioning

confidence: 99%

Trop2: Jack of All Trades, Master of None

Lenárt

Šmarda

et al. 2020

Cancers

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Trophoblast cell surface antigen 2 (Trop2) is a widely expressed glycoprotein and an epithelial cell adhesion molecule (EpCAM) family member. Although initially identified as a transmembrane protein, other subcellular localizations and processed forms were described. Its congenital mutations cause a gelatinous drop-like corneal dystrophy, a disease characterized by loss of barrier function in corneal epithelial cells. Trop2 is considered a stem cell marker and its expression associates with regenerative capacity in various tissues. Trop2 overexpression was described in tumors of different origins; however, functional studies revealed both oncogenic and tumor suppressor roles. Nevertheless, therapeutic potential of Trop2 was recognized and clinical studies with drug–antibody conjugates have been initiated in various cancer types. One of these agents, sacituzumab govitecan, has been recently granted an accelerated approval for therapy of metastatic triple-negative breast cancer. In this article, we review the current knowledge about the yet controversial function of Trop2 in homeostasis and pathology.

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“…; McDougall et al . ). In the rat, IUGR leads to delayed neuronal migration in the cerebral cortex (Sasaki et al .…”

Section: Introductionmentioning

confidence: 97%

Development of the cerebral cortex and the effect of the intrauterine environment

Quezada

Castillo‐Melendez

Walker

et al. 2018

The Journal of Physiology

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The human brain is one of the most complex structures currently under study. Its external shape is highly convoluted, with folds and valleys over the entire surface of the cortex. Disruption of the normal pattern of folding is associated with a number of abnormal neurological outcomes, some serious for the individual. Most of our knowledge of the normal development and folding of the cerebral cortex (gyrification) focuses on the internal, biological (i.e. genetically driven) mechanisms of the brain that drive gyrification. However, the impact of an adverse intrauterine and maternal physiological environment on cortical folding during fetal development has been understudied. Accumulating evidence suggests that the state of the intrauterine and maternal environment can have a significant impact on gyrification of the fetal cerebral cortex. This review summarises our current knowledge of how development in a suboptimal intrauterine and maternal environment can affect the normal development of the folded cerebral cortex. Abstract figure legendCommon pregnancy-related conditions such as intrauterine growth restriction (IUGR), preterm birth, hypoxia, maternal/fetal infections and multiple fetuses, can have an impact on the normal development and folding of the cerebral cortex.

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Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum

Cited by 22 publications

References 58 publications

Intrauterine Growth Restriction Affects Cerebellar Granule Cells in the Developing Guinea Pig Brain

Intrauterine Growth Restriction Affects Cerebellar Granule Cells in the Developing Guinea Pig Brain

Trop2: Jack of All Trades, Master of None

Development of the cerebral cortex and the effect of the intrauterine environment

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