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Related Experiment Videos

Human wild-type alpha-synuclein impairs neurogenesis.

Beate Winner1, D Chichung Lie, Edward Rockenstein

  • 1Department of Neurology, University of Regensburg, Regensburg, Germany.

Journal of Neuropathology and Experimental Neurology
|December 8, 2004
PubMed
Summary

Alpha-synuclein accumulation in synucleinopathies impairs adult neurogenesis, reducing neuronal survival in the olfactory bulb and hippocampus. This may contribute to olfactory deficits in these neurodegenerative diseases.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Neurodegenerative Diseases

Background:

  • Synucleinopathies are neurodegenerative diseases defined by alpha-synuclein inclusions.
  • Alpha-synuclein aggregates in neurons and glial cells, including brain regions with adult neurogenesis.

Purpose of the Study:

  • To investigate the pathophysiological role of alpha-synuclein in adult neurogenesis.
  • To examine the impact of human alpha-synuclein overexpression on neuronal cell birth and survival in adult mice.

Main Methods:

  • Overexpression of human wild-type alpha-synuclein in adult mice using the platelet-derived growth factor promoter.
  • Analysis of cell proliferation and neuronal fate in the olfactory bulb and hippocampal dentate gyrus.

Main Results:

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  • No significant effect on cell proliferation was detected.
  • Significantly reduced neurogenesis and fewer neurons were observed in the olfactory bulb and hippocampus.
  • The primary cause was diminished survival of neuronal precursors in neurogenic regions.

Conclusions:

  • Alpha-synuclein overexpression disrupts the balance of neuronal cell birth and death in adult neurogenic regions.
  • Reduced adult neurogenesis in the olfactory bulb may underlie olfactory deficits seen in synucleinopathies.
  • These findings suggest a novel mechanism contributing to neurodegeneration progression.