Identification of divergent organ-specific gene and protein expression signatures for mitochondrial function, inflammatory response, and proteostasis in the liver and brain in the rotenone-induced rat model of Parkinson's disease.

Authors

Tuba Oz, Juan Fraile-Ramos, Radosław Kujawski, Olga Wojciechowska, Marta Karaźniewicz-Łada, Przemysław Łukasz Mikołajczak, Lydia Giménez-Llort, Małgorzata Kujawska

Published in

Molecular biology reports. Volume 53. Issue 1. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Emerging evidence suggests that peripheral organs, particularly the liver, may influence brain homeostasis and neurodegenerative diseases. This study investigates the differential expression of Parkinson's disease (PD)-related, oxidative stress, and inflammatory genes in the liver and brain of six-week-old male albino Wistar rats (250-300 g) subchronically exposed to rotenone (ROT, 1.3 mg/kg/day, 35 days, b.w.), a pesticide commonly used to model PD. Relative expression levels were measured using quantitative real-time PCR (RT-qPCR) and western blot. Genes involved in mitophagy (Parkin (PARK2), p = 0.0039), oxidative stress response (Parkinson's disease protein (DJ-1), p = 0.0209), lysosomal function (Low-density lipoprotein receptor-related protein-1 (LRP1), p = 0.0418; ATPase cation transporting 13a2 (ATP13a2), p = 0.0308), and inflammation (Tumour necrosis factor alpha (TNF-α), p = 0.0171) were found upregulated in the brain of ROT-induced rats as compared to control rats, and were also significantly higher than in the liver (p < 0.05). In contrast, significantly higher phosphatase and tensin homolog-induced kinase 1 (PINK1) expression was found in the liver as compared to the brain (p = 0.0198). Notably, these inter-organ differences and transcriptional shifts were absent in the controls. Moreover, the liver exhibited distinct molecular responses, including significant downregulation of ATP13a2 and SNCA (Encoding alpha-synuclein) and overexpression of NFe2-like basic leucine zipper transcription factor 2 (NFe2l2), compared to control rats (p < 0.05). Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and interferon gamma (IFN-γ) showed no significant changes in either tissue (p > 0.05). These findings demonstrate that distinct molecular alterations in the liver and brain following ROT treatment, including differences in the regulation of genes associated with mitophagy, oxidative stress, proteostasis, and inflammation. Our findings demonstrate tissue-specific molecular associations in the liver and brain within the ROT-induced PD model, providing new insights into the pathophysiology of neurodegeneration and identifying potential biomarkers and therapeutic targets for future studies.

PMID:
42467129
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.