Neurodevelopmental wiring deficits in the Ts65Dn mouse model of Down syndrome
| Autor: | Wilson C. J. Chung, Christina A. Watts, Kristy Welshhans, Shruti Jain |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Down syndrome Neurogenesis Neuronal Outgrowth Fornix Brain Hippocampus Anterior commissure Mice Transgenic Hippocampal formation Biology In Vitro Techniques Corpus callosum Corpus Callosum 03 medical and health sciences Mice 0302 clinical medicine Intellectual disability Neural Pathways medicine Animals Axon Anterior Commissure Brain Cell Size Neurons General Neuroscience Organ Size medicine.disease Axons Axon Guidance Disease Models Animal 030104 developmental biology medicine.anatomical_structure Animals Newborn Axon guidance Down Syndrome Trisomy Chromosome 21 Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience letters. 714 |
| ISSN: | 1872-7972 |
| Popis: | Down syndrome is the most common genetic cause of intellectual disability and occurs due to the trisomy of human chromosome 21. Adolescent and adult brains from humans with Down syndrome exhibit various neurological phenotypes including a reduction in the size of the corpus callosum, hippocampal commissure and anterior commissure. However, it is unclear when and how these interhemispheric connectivity defects arise. Using the Ts65Dn mouse model of Down syndrome, we examined interhemispheric connectivity in postnatal day 0 (P0) Ts65Dn mouse brains. We find that there is no change in the volume of the corpus callosum or anterior commissure in P0 Ts65Dn mice. However, the volume of the hippocampal commissure is significantly reduced in P0 Ts65Dn mice, and this may contribute to the impaired learning and memory phenotype of this disorder. Interhemispheric connectivity defects that arise during development may be due to disrupted axon growth. In line with this, we find that developing hippocampal neurons display reduced axon length in vitro, as compared to neurons from their euploid littermates. This study is the first to report the presence of defective interhemispheric connectivity at the time of birth in Ts65Dn mice, providing evidence that early therapeutic intervention may be an effective time window for the treatment of Down syndrome. |
| Databáze: | OpenAIRE |
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