Thrombospondin-1 (TSP-1) and Neuronal Plasticity: Implications in Down Syndrome
Main Article Content
Abstract
Down syndrome is the most common genetic cause of intellectual disability. Nevertheless, under certain stimulation processes, Down syndrome people can develop certain intellectual skills, suggesting an active mechanism of neuronal plasticity. Defects in both dendritic arborization and dendritic spines could affect neuronal plasticity and contribute to the degree of intellectual disability in people with Down syndrome. However, the cellular mechanisms involved in this process are unknown. Thrombospondin-1 (TSP-1) is an astrocyte-secreted protein involved in the development and maintenance of dendritic spines and synapses, which is altered in Down syndrome. Nonetheless, the role of TSP-1 in neuronal plasticity is not well characterized. In this study, we analyze whether TSP-1 is involved in neuronal microstructure changes induced by environmental enrichment, a model of experience-dependent neuronal plasticity. We found that the increase in dendritic spine density induced by environmental enrichment is associated with an increase in TSP-1 levels in the hippocampus of wild-type mice. The lack of TSP-1 in TSP-1-/- mice produce changes in the number and length of dendritic branches and a decrease in both, the number of intersections and density of dendritic spines. Exposure of TSP-1-/- mice to environmental enrichment did not affect the dendritic length and branching and number of intersections, but increased the density of dendritic spines significantly. These results suggest a role of TSP-1 as an important factor regulating brain microstructural plasticity, whose activity is reduced in Down syndrome.
Keywords:
thrombospondin-1 (TSP-1), dendritic spines, enriched environments, neuronal plasticity, Down syndrome
Article Details
How to Cite
GARCIA, Octavio; VILLEGAS-PIÑA, Jesús Antonio; VILLEGAS-PIÑA, Jesús Antonio.
Thrombospondin-1 (TSP-1) and Neuronal Plasticity: Implications in Down Syndrome.
Medical Research Archives, [S.l.], v. 10, n. 10, oct. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3168>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v10i10.3168.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Carlesimo GA, Marotta L, Vicari S. Long-term memory in mental retardation: evidence for a specific impairment in subjects with Down's syndrome Neuropsychol. 1997;35:71-79. doi: 10.1016/s0028-3932(96)00055-3
4. Chapman RS, Hesketh LJ. Behavioral phenotype of individuals with Down syndrome. Ment Retard Dev Disabil Res Rev. 2000;6:84-95. doi: 10.1002/1098-2779(2000)6:2<84::AID-MRDD2>3.0.CO;2-P
5. Angulo-Chavira AQ, García O, Arias-Trejo N. Pupil response and attention skills in Down syndrome. Res Dev Disabil. 2017;70:40-49. doi: 10.1016/j.ridd.2017.08.011
6. Vicari S. Motor development and neuropsychological patterns in persons with Down syndrome. Behav Genet. 2006;36:355-364. doi: 10.1007/s10519-006-9057-8
7. Dierssen M. Down syndrome: the brain in trisomic mode. Nat Rev Neurosci. 2012;13:844-858. doi: 10.1038/nrn3314
8. Ponroy Bally B, Murai KK. Astrocytes in Down Syndrome Across the Lifespan. Front Cell Neurosci. 2021;15:702685. doi: 10.3389/fncel.2021.702685.
9. Garcia O, Flores-Aguilar L. Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer's disease. Front Cell Neurosci. 2022;16:987212. doi: 10.3389/fncel.2022.987212
10. Olmos-Serrano JL, Kang HJ, Tyler WA, et al. Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination. Neuron. 2016;89:1208-1222. doi: 10.1016/j.neuron.2016.01.042.
11. Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 2006;7:697-709. doi: 10.1038/nrn1970
12. Kempermann G. Environmental enrichment, new neurons and the neurobiology of individuality. Nat Rev Neurosci. 2019;20:235-245. doi: 10.1038/s41583-019-0120-x.
13. Hirase H, Shinohara Y. Transformation of cortical and hippocampal neural circuit by environmental enrichment. Neurosci. 2014;280:282-298. doi: 10.1016/j.neuroscience.2014.09.031
14. Moser MB, Trommald M, Egeland T, et al. Spatial training in a complex environment and isolation alter the spine distribution differently in rat CA1 pyramidal cells. J Comp Neurol. 1997;380(3):373-381. doi: 10.1002/(sici)1096-9861(19970414)380:3<373::aid-cne6>3.0.co;2-#
15. Sutherland R, Gibb R, Kolb B. The hippocampus makes a significant contribution to experience-dependent neocortical plasticity. Behav Brain Res. 2010;214:121-124. doi: 10.1016/j.bbr.2010.05.051.
16. Gelfo F, De Bartolo P, Giovine A, et al. Layer and regional effects of environmental enrichment on the pyramidal neuron morphology of the rat. Neurobiol Learn Mem. 2009;91:353-365.
17. Landers MS, Knott GW, Lipp HP, et al. Synapse formation in adult barrel cortex following naturalistic environmental enrichment. Neurosci. 2011;199:143-152. doi: 10.1016/j.neuroscience.2011.10.040.
18. Martin YB, Negredo P, Avendaño C. Experience-dependent plasticity in early stations of sensory processing in mature brains: effects of environmental enrichment on dendrite measures in trigeminal nuclei. Brain Struct Funct. 2022;227:865-879. doi: 10.1007/s00429-021-02424-3.
19. Hines S, Bennett F. Effectiveness of early interventions for children with Down syndrome. Ment Retard Dev Disabil Res Rev. 1996;2:96-101
20. Dierssen M, Benavides-Piccione R, Martínez-Cué C, et al. Alterations of neocortical pyramidal cell phenotype in the Ts65Dn mouse model of Down syndrome: effects of environmental enrichment. Cereb Cortex. 2003;13:758-764. doi:10.1093/cercor/13.7.758
21. De Giorgio A. The roles of motor activity and environmental enrichment in intellectual disability. Somatosens Mot Res. 2017;34:34-43. doi: 10.1080/08990220.2016.1278204
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