Abstract
A rapid growth in human cerebellar development occurs in the third trimester, which is impeded by preterm delivery. The goal of this study was to characterize the impact of preterm delivery on the developmental program of the human cerebellum. Still born infants, which meant that all development up to that age had taken place in-utero, were age paired with preterm delivery infants, who had survived in an ex-utero environment, which meant that their development had also taken place outside the uterus. The two groups were assessed on quantitative measures that included molecular markers of granule neuron, purkinje neuron and bergmann glia differentiation, as well as the expression of the sonic hedgehog signaling pathway, that is important for cerebellar growth. We report that premature birth and development in an ex-utero environment leads to a significant decrease in the thickness and an increase in the packing density of the cells within the external granular layer and the inner granular layer well, as a reduction in the density of bergmann glial fibres. In addition, this also leads to a reduced expression of sonic hedgehog in the purkinje layer. We conclude that the developmental program of the cerebellum is specifically modified by events that follow preterm delivery.
Highlights
The cerebellum is acknowledged as being important for motor coordination, and for abstract mental processes such as thought [1,2,3,4,5,6,7]
A rapid growth in cerebellum development takes place in the third trimester [14,15]. This is in striking contrast to the development of the cerebellum in the commonly used animal model system, the rodent, in which the cerebellum is relatively immature at birth, and the proliferation of the external granular layer (EGL), the formation of the internal granular layer (IGL) and foliation occur postnatally [16]
This study describes for the first time changes that occur at the cellular level and suggests potential mechanisms for perturbations in cerebellum development that occur after preterm delivery
Summary
The cerebellum is acknowledged as being important for motor coordination, and for abstract mental processes such as thought [1,2,3,4,5,6,7]. Perturbations in cerebellum development can result in cognitive deficits [8,9,10,11,12]. In this regard, several mental disorders have been correlated with cerebellar dysfunction. A rapid growth in cerebellum development takes place in the third trimester [14,15]. This is in striking contrast to the development of the cerebellum in the commonly used animal model system, the rodent, in which the cerebellum is relatively immature at birth, and the proliferation of the external granular layer (EGL), the formation of the internal granular layer (IGL) and foliation occur postnatally [16]. MRI studies have shown that this rapid growth in the third trimester is impeded by preterm delivery, where childbirth occurs at a period less than 37 completed weeks of gestation, resulting in a smaller cerebellum [15,17,18,19]
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