Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons

Molecular Neurodegeneration

Robert H Schiestl²  Marie-Francoise Chesselet³  Eliezer Masliah¹  Franziska Richter³  Sheila M Fleming³  Yofre Cabeza-Arvelaiz² 

[1] Department of Neurosciences, University of California, San Diego; 9500 Gilman Drive, La Jolla, CA 92093, USA;Department of Pathology and Environmental Health Sciences, The Geffen School of Medicine and School of Public Health, University of California, Los Angeles, 650 Charles E. Young Dr. S, CHS 71-295; Los Angeles, CA 90095, USA;Department of Neurology, The Geffen School of Medicine, University of California, Los Angeles, 710 Westwood plaza, Los Angeles, CA 90095, USA

关键词: diabetes;    vesicle release;    synaptic plasticity;    Alzheimer's disease;    Parkinson's disease;    neuroprotection;    apoptosis;    α-synuclein;   

Others  :  863998
DOI  :  10.1186/1750-1326-6-83

 received in 2011-06-10, accepted in 2011-12-13,  发布年份 2011

【 摘 要 】

Background

Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinson's disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD.

Results

The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis.

Conclusion

The results support a key role for SNCA in synaptic function and revealed an apoptotic signature in Thy1-aSyn mice, which together with specific alterations of neuroprotective genes suggest the activation of adaptive compensatory mechanisms that may protect striatal neurons in conditions of neuronal overexpression of SNCA.

【 授权许可】

   
2011 Cabeza-Arvelaiz et al; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

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