Upregulated DNA Damage-Linked Biomarkers in Parkinson's Disease Model Mice

Autor: Fei Zeng, Karsten Parker, Yanqiang Zhan, Matthew Miller, Meng-Yang Zhu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: ASN Neuro, Vol 15 (2023)
Druh dokumentu: article
ISSN: 1759-0914
17590914
DOI: 10.1177/17590914231152099
Popis: Oxidative stress-induced DNA damage has been considered to constitute a unifying pathogenesis in the development of Parkinson's disease (PD). In the present study, multiple measurement methods were applied to examine the expression of DNA damage markers in the brain of the vesicular monoamine transporter 2 transgenic mice (VMAT2 Lo), a PD animal model. The results demonstrated that mainly in the substantia nigra (SN) and locus coeruleus (LC) of VMAT2 Lo mice at the ages of 18 and 23 months, there was a significant increase in the protein levels of phosphor-ataxia telangiectasia mutated (pATM), as well as ATM and RAD 3-related (pATR) two DNA damage sensors, and γ-H2A histone family member X (γ-H2AX), a DNA damage marker of double-strand breaks (DSBs). Furthermore, these alterations were accompanied by a significant elevation of mRNA and protein levels of Cav1.2 and Cav1.3, two voltage-gated Ca 2+ channel proteins, and modulator of calcium homeostasis in the SN and LC. Finally, the measurements of TUNEL assay and immunostaining in the brain regions confirmed the presence of apoptosis and a marked increase of immunoreactive 8-oxo-7,8-dihydro-2′dihydroguanosine (8-OHdG) and p53-binding protein 1 (53BP1), two DNA lesion indicators induced by oxidative stress. These novel findings are coincident with the observations previously reported in PD patients and PD animal models, and provide the evidence for the features of DNA damage involved in pathogenesis of PD and feasibility of this model for investigation of PD. Summary Statement The present study examined expression of DNA damage markers in VMAT2 Lo PD model mice. The results demonstrate there is a significant increase in these DNA damage markers mostly in the brain regions of 18- and 23-month-old model mice, indicating oxidative stress-induced DNA lesion is an important pathologic feature of this mouse model.
Databáze: Directory of Open Access Journals
Externí odkaz: