Research Paper Volume 13, Issue 4 pp 6103—6114

Functional analysis of brain derived neurotrophic factor (BDNF) in Huntington’s disease

Zhike Zhou1, , Shanshan Zhong2, , Rongwei Zhang1, , Kexin Kang1, , Xiaoqian Zhang2, , Ying Xu3,4, , Chuansheng Zhao2, *, , Mei Zhao5, *, ,

  • 1 Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning, PR China
  • 2 Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning, PR China
  • 3 Computational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, The University of Georgia, Athens, GA 30602, USA
  • 4 Cancer Systems Biology Center, The China-Japan Union Hospital, Jilin University, Changchun, PR China
  • 5 Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang 110004, Liaoning, PR China
* Equal contribution

Received: August 24, 2020       Accepted: October 31, 2020       Published: February 25, 2021
How to Cite

Copyright: © 2021 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The aim of this study is to determine the molecular functions of brain derived neurotrophic factor (BDNF) in Huntington’s disease (HD). A total of 1,675 differentially expressed genes (DEGs) were overlapped from HD versus control and BDNF-low versus high groups. Five co-expression modules were constructed using weight gene correlation network analysis, among which the blue and turquoise modules were most strongly correlated with HD and low BDNF. Functional enrichment analyses revealed DEGs in these modules significantly enriched in GABAergic synapse, phagosome, cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), renin-angiotensin system (Ras), Ras-associated protein-1 and retrograde endocannabinoid signaling pathways. The intersection pathways of BDNF, such as cAMP, MAPK and Ras signaling pathways, were identified in global regulatory network. Further performance evaluation of low BDNF accurately predicted HD occurrence according to the area under the curve of 82.4%. In aggregate, our findings highlighted the involvement of low BDNF expression in HD pathogenesis, potentially mediated by cAMP, MAPK and Ras signaling pathways.


ACE: angiotensin converting enzyme; Ang II: angiotensin II; AUC: area under the curve; BDNF: brain derived neurotrophic factor; cAMP: cyclic adenosine monophosphate; DEGs: differentially expressed genes; FDR: false discovery rate; GEO: Gene Expression Omnibus; GS: gene significance; GSEA: gene set enrichment analysis; HD: Huntington’s disease; KEGG: Kyoto Encyclopedia of Genes and Genomes; logFC: logarithm fold change; MAPK: mitogen-activated protein kinase; mHtt: mutant huntingtin; MM: module membership; Ras: renin-angiotensin system; Rap1: Ras-associated protein-1; RNA: ribose nucleic acid; ROC: Receiver operating characteristic; STRING: Search Tool for the Retrieval of Interacting Genes; WGCNA: weight gene correlation network analysis.