Post-symptomatic Delivery of Brain-Derived Neurotrophic Factor (BDNF) Ameliorates Spinocerebellar Ataxia Type 1 (SCA1) Pathogenesis

Carrie Sheeler, Juao Guilherme Rosa, Ella Borgenheimer, Aaron Mellesmoen, Orion Rainwater, Marija Cvetanovic

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an abnormal expansion of CAG repeats in the Ataxin1 (ATXN1) gene. SCA1 is characterized by motor deficits, cerebellar neurodegeneration, and gliosis and gene expression changes. Expression of brain-derived neurotrophic factor (BDNF), growth factor important for the survival and function of cerebellar neurons, is decreased in ATXN1[82Q] mice, the Purkinje neuron specific transgenic mouse model of SCA1. As this decrease in BDNF expression may contribute to cerebellar neurodegeneration, we tested whether delivery of extrinsic human BDNF via osmotic ALZET pumps has a beneficial effect on disease severity in this mouse model of SCA1. Additionally, to test the effects of BDNF on established and progressing cerebellar pathogenesis and motor deficits, we delivered BDNF post-symptomatically. We have found that post-symptomatic delivery of extrinsic BDNF ameliorated motor deficits and cerebellar pathology (i.e., dendritic atrophy of Purkinje cells, and astrogliosis) indicating therapeutic potential of BDNF even after the onset of symptoms in SCA1. However, BDNF did not alter Purkinje cell gene expression changes indicating that certain aspects of disease pathogenesis cannot be ameliorated/slowed down with BDNF and that combinational therapies may be needed.

Original languageEnglish (US)
Pages (from-to)420-429
Number of pages10
Issue number3
Early online dateJan 4 2021
StatePublished - Jun 2021

Bibliographical note

Funding Information:
This study is funded by the Regenerative Medicine Minnesota (RMM 101617 TR 001) and National Institutes of Health (NS107387-02) grants.

Funding Information:
We are grateful to Drs. Harry Orr and Huda Zoghbi for the generous gift of mice and to all the members of Cvetanovic and Orr laboratories for suggestions.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.


  • ATAXIN-1
  • BDNF
  • Cerebellar ataxia
  • Gliosis
  • Neurodegeneration
  • Purkinje cells

PubMed: MeSH publication types

  • Journal Article


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