PXD039728

PXD039728 is an original dataset announced via ProteomeXchange.

Title	Copper exposure aggravates motor phenotype via inhibiting mitophagy in SOD1G93A transgenic mice
Description	Background Amyotrophic lateral sclerosis (ALS) is an age-dependent and incurable neurodegenerative disease. It is pathologically characterized by selective degeneration of motor neurons resulting in a catastrophic loss of motor function. Previous studies showed that excess copper (Cu) might have a role in ALS etiology. However, the underlying mechanism remains incompletely elucidated. Therefore, we aimed to investigate the neurotoxicity and underlying mechanism of Cu exposure in female ALS mice with SOD1G93A gene mutation. Methods After three months of treatment with low-dose Cu exposure (0.13 PPM copper chloride drinking water), the motor ability was assessed by various behavioral methods, including climbing-pole test, rotarod test, hanging endurance test, grip strength test and gait analysis. Muscle atrophy and fibrosis were evaluated by histopathology. The proliferation of astrocytes and microglia was assessed by immunohistochemical analysis. The number of motor neurons in the spinal cord was determined by Nissl staining and ChAT immunohistochemical staining. Western blotting and proteomics revealed the effect of Cu exposure on mitochondrial protein expression in mice. Results Behavioral tests showed that Cu exposure worsened motor function in SOD1G93A mice. Compared with SOD1G93A transgenic mice, there was no significant difference in the pole-climbing test after Cu exposure (P =0.6156). There were significant changes in rotarod test, hanging endurance test and grip strength test (P =0.0121; P = 0.0085; P =0.0105). At the same time, Cu exposure aggravated muscle fibrosis and the loss of spinal motor neurons (P <0.05) and was associated with neuroinflammation (P <0.05). The proteomic analysis further showed that differentially expressed proteins among wild-type mice (WT), ALS mice, and Cu-treated ALS mice were mainly involved in muscle contraction, ATP metabolic processes, immune responses, peroxisomes, mitochondrial electrons respiratory transport chain, GMP biological processes, and were co-related with disturbances in energy metabolism, which was reflected in mitochondrial dysfunction in ALS mice. In addition, Western Blot showed that Cu exposure decreased the expression of mitochondria-related proteins (P <0.05), which was consistent with the results of proteomic analysis. Conclusions In conclusion, our findings showed that Cu exposure aggravates motor dysfunction and pathological changes in ALS mice via mitochondrial dysfunction.
HostingRepository	iProX
AnnounceDate	2023-01-29
AnnouncementXML	Submission_2023-01-28_19:42:19.383.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Huan Zhang
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-28 19:42:04	ID requested
⏵ 1	2023-01-28 19:42:19	announced

Dataset with its publication pending

submitter keyword: Amyotrophic lateral sclerosis, copper, mitophagy, Motor performance

Xifei Yang
contact affiliation	Shenzhen Center for Disease Control and Prevention
contact email	xifeiyang@gmail.com
lab head
Huan Zhang
contact affiliation	School of Public Health, University of South China&Shenzhen Center for Disease Control and Prevention
contact email	997548308@qq.com
dataset submitter

iProX dataset URI