Transient biochemical compartmentalization of Purkinje cells during early cerebellar development

1985 ◽  
Vol 111 (1) ◽  
pp. 129-137 ◽  
Author(s):  
Marion Wassef ◽  
Jean Pierre Zanetta ◽  
Arlette Brehier ◽  
Constantino Sotelo
2020 ◽  
Vol 10 (12) ◽  
pp. 897
Author(s):  
Tara Barron ◽  
Jun Hee Kim

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.


2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Yoshinobu Kawamura ◽  
Hisako Nakayama ◽  
Kouichi Hashimoto ◽  
Kenji Sakimura ◽  
Kazuo Kitamura ◽  
...  

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Ying Huang ◽  
Qiong Zhang ◽  
Ning-Ning Song ◽  
Lei Zhang ◽  
Yu-Ling Sun ◽  
...  

2004 ◽  
Vol 25 (1) ◽  
pp. 138-152 ◽  
Author(s):  
Jiankai Luo ◽  
Ullrich Treubert-Zimmermann ◽  
Christoph Redies

1996 ◽  
Vol 92 (2) ◽  
pp. 140-146 ◽  
Author(s):  
Suzanne Chen ◽  
Yu Qin Ren ◽  
Dean E. Hillman

2020 ◽  
Vol 10 (8) ◽  
pp. 475 ◽  
Author(s):  
Daniel Chizhikov ◽  
Randal K. Buddington ◽  
Igor Y. Iskusnykh

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.


2017 ◽  
Vol 232 (2) ◽  
pp. 259-272 ◽  
Author(s):  
Joke Delbaere ◽  
Pieter Vancamp ◽  
Stijn L J Van Herck ◽  
Nele M A Bourgeois ◽  
Mary J Green ◽  
...  

Inactivating mutations in the human SLC16A2 gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) result in the Allan–Herndon–Dudley syndrome accompanied by severe locomotor deficits. The underlying mechanisms of the associated cerebellar maldevelopment were studied using the chicken as a model. Electroporation of an MCT8-RNAi vector into the cerebellar anlage of a 3-day-old embryo allowed knockdown of MCT8 in Purkinje cell precursors. This resulted in the downregulation of the thyroid hormone-responsive gene RORα and the Purkinje cell-specific differentiation marker LHX1/5 at day 6. MCT8 knockdown also results in a smaller and less complex dendritic tree at day 18 suggesting a pivotal role of MCT8 for cell-autonomous Purkinje cell maturation. Early administration of the thyroid hormone analogue 3,5,3′-triiodothyroacetic acid partially rescued early Purkinje cell differentiation. MCT8-deficient Purkinje cells also induced non-autonomous effects as they led to a reduced granule cell precursor proliferation, a thinner external germinal layer and a loss of PAX6 expression. By contrast, at day 18, the external germinal layer thickness was increased, with an increase in presence of Axonin-1-positive post-mitotic granule cells in the initial stage of radial migration. The concomitant accumulation of presumptive migrating granule cells in the molecular layer, suggests that inward radial migration to the internal granular layer is stalled. In conclusion, early MCT8 deficiency in Purkinje cells results in both cell-autonomous and non-autonomous effects on cerebellar development and indicates that MCT8 expression is essential from very early stages of development, providing a novel insight into the ontogenesis of the Allan–Herndon–Dudley syndrome.


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