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Developmental delay in motor skill acquisition in Niemann-Pick C1 mice reveals abnormal cerebellar morphogenesis

Overview of attention for article published in Acta Neuropathologica Communications, September 2016
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Title
Developmental delay in motor skill acquisition in Niemann-Pick C1 mice reveals abnormal cerebellar morphogenesis
Published in
Acta Neuropathologica Communications, September 2016
DOI 10.1186/s40478-016-0370-z
Pubmed ID
Authors

Paola Caporali, Francesco Bruno, Giampiero Palladino, Jessica Dragotto, Laura Petrosini, Franco Mangia, Robert P. Erickson, Sonia Canterini, Maria Teresa Fiorenza

Abstract

Niemann-Pick type C1 (NPC1) disease is a lysosomal storage disorder caused by defective intracellular trafficking of exogenous cholesterol. Purkinje cell (PC) degeneration is the main sign of cerebellar dysfunction in both NPC1 patients and animal models. It has been recently shown that a significant decrease in Sonic hedgehog (Shh) expression reduces the proliferative potential of granule neuron precursors in the developing cerebellum of Npc1 (-/-) mice. Pursuing the hypothesis that this developmental defect translates into functional impairments, we have assayed Npc1-deficient pups belonging to the milder mutant mouse strain Npc1 (nmf164) for sensorimotor development from postnatal day (PN) 3 to PN21. Npc1 (nmf164) / Npc1 (nmf164) pups displayed a 2.5-day delay in the acquisition of complex motor abilities compared to wild-type (wt) littermates, in agreement with the significant disorganization of cerebellar cortex cytoarchitecture observed between PN11 and PN15. Compared to wt, Npc1 (nmf164) homozygous mice exhibited a poorer morphological differentiation of Bergmann glia (BG), as indicated by thicker radial shafts and less elaborate reticular pattern of lateral processes. Also BG functional development was defective, as indicated by the significant reduction in GLAST and Glutamine synthetase expression. A reduced VGluT2 and GAD65 expression also indicated an overall derangement of the glutamatergic/GABAergic stimulation that PCs receive by climbing/parallel fibers and basket/stellate cells, respectively. Lastly, Npc1-deficiency also affected oligodendrocyte differentiation as indicated by the strong reduction of myelin basic protein. Two sequential 2-hydroxypropyl-β-cyclodextrin administrations at PN4 and PN7 counteract these defects, partially preventing functional impairment of BG and fully restoring the normal patterns of glutamatergic/GABAergic stimulation to PCs.These findings indicate that in Npc1 (nmf164) homozygous mice the derangement of synaptic connectivity and dysmyelination during cerebellar morphogenesis largely anticipate motor deficits that are typically observed during adulthood.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 2%
Unknown 52 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 21%
Student > Ph. D. Student 7 13%
Other 6 11%
Student > Bachelor 6 11%
Student > Master 5 9%
Other 7 13%
Unknown 11 21%
Readers by discipline Count As %
Neuroscience 12 23%
Biochemistry, Genetics and Molecular Biology 10 19%
Medicine and Dentistry 5 9%
Veterinary Science and Veterinary Medicine 2 4%
Nursing and Health Professions 2 4%
Other 9 17%
Unknown 13 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 October 2017.
All research outputs
#17,814,957
of 22,886,568 outputs
Outputs from Acta Neuropathologica Communications
#1,201
of 1,383 outputs
Outputs of similar age
#244,065
of 337,400 outputs
Outputs of similar age from Acta Neuropathologica Communications
#25
of 30 outputs
Altmetric has tracked 22,886,568 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,383 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 10th percentile – i.e., 10% of its peers scored the same or lower than it.
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We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.