Open AccessTranscriptomic approach predicts a major role for transforming growth factor beta type 1 pathway in L‐Dopa ‐induced dyskinesia in parkinsonian rats
Author(s) -
Dyavar Shetty Ravi,
Potts Lisa F.,
Beck Goichi,
Dyavar Shetty Bhagya Laxmi,
Lawson Benton,
Podany Anthony T.,
Fletcher Courtney V.,
Amara Rama Rao,
Papa Stella M.
Publication year - 2020
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/gbb.12690
Subject(s) - transcriptome , downregulation and upregulation , dyskinesia , transforming growth factor , biology , gene , transforming growth factor beta , parkinson's disease , regulator , mapk/erk pathway , cancer research , disease , microbiology and biotechnology , signal transduction , gene expression , genetics , medicine
Dyskinesia induced by long‐term L‐Dopa (LID) therapy in Parkinson disease is associated with altered striatal function whose molecular bases remain unclear. Here, a transcriptomic approach was applied for comprehensive analysis of distinctively regulated genes in striatal tissue, their specific pathways, and functional‐ and disease‐associated networks in a rodent model of LID. This approach has identified transforming growth factor beta type 1 (TGFβ1) as a highly upregulated gene in dyskinetic animals. TGFβ1 pathway is a top aberrantly regulated pathway in the striatum following LID development based on differentially expressed genes (> 1.5 fold change and P < 0.05). The induction of TGFβ1 pathway specific genes, TGFβ1 , INHBA , AMHR2 and PMEPA1 was also associated with regulation of NPTX2 , PDP1 , SCG2 , SYNPR , TAC1 , TH , TNNT1 genes. Transcriptional network and upstream regulator analyses have identified AKT‐centered functional and ERK‐centered disease networks revealing the association of TGFβ1 , IL‐1β and TNFα with LID development. Therefore, results support that TGFβ1 pathway is a major contributor to the pathogenic mechanisms of LID.