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Chronic sleep restriction in the rotenone Parkinson's disease model in rats reveals peripheral early-phase biomarkers.

ABSTRACT: Parkinson's disease (PD) is a chronic disorder that presents a range of premotor signs, such as sleep disturbances and cognitive decline, which are key non-motor features of the disease. Increasing evidence of a possible association between sleep disruption and the neurodegenerative process suggests that sleep impairment could produce a detectable metabolic signature on the disease. In order to integrate neurocognitive and metabolic parameters, we performed untargeted and targeted metabolic profiling of the rotenone PD model in a chronic sleep restriction (SR) (6?h/day for 21 days) condition. We found that SR combined with PD altered several behavioural (reversal of locomotor activity impairment; cognitive impairment; delay of rest-activity rhythm) and metabolic parameters (branched-chain amino acids, tryptophan pathway, phenylalanine, and lipoproteins, pointing to mitochondrial impairment). If combined, our results bring a plethora of parameters that represents reliable early-phase PD biomarkers which can easily be measured and could be translated to human studies.

SUBMITTER: Fagotti J

PROVIDER: S-EPMC6374389 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Chronic sleep restriction in the rotenone Parkinson's disease model in rats reveals peripheral early-phase biomarkers.

Fagotti Juliane J Targa Adriano D S ADS Rodrigues Lais S LS Noseda Ana Carolina D ACD Dorieux Flávia W C FWC Scarante Franciele F FF Ilkiw Jessica L JL Louzada Fernando M FM Chowdhury Namrata R NR van der Veen Daan R DR Middleton Benita B Pennings Jeroen L A JLA Swann Jonathan R JR Skene Debra J DJ Lima Marcelo M S MMS

Scientific reports 20190213 1

Parkinson's disease (PD) is a chronic disorder that presents a range of premotor signs, such as sleep disturbances and cognitive decline, which are key non-motor features of the disease. Increasing evidence of a possible association between sleep disruption and the neurodegenerative process suggests that sleep impairment could produce a detectable metabolic signature on the disease. In order to integrate neurocognitive and metabolic parameters, we performed untargeted and targeted metabolic prof ...[more]

PMID: 30760786

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Project description:The adverse effects of sleep disorders on male fertility are increasingly concerning. In this study, a rat model of chronic sleep restriction (CSR) was established using the modified multiplatform method. The effects of CSR on the fertility of male rats were evaluated first based on sexual behavior. Serum hormones, including testosterone (T), prolactin (PRL), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and sperm parameters (concentration, viability, motility, deformation rate) were measured, and testicular histology was analysed by hematoxylin and eosin staining. The transcriptional differences between CSR rats and control rats were detected by RNA sequencing (RNA-Seq), and DNA methylation was then detected by bisulfite sequencing. After the differently expressed genes of CSR rats were sequenced and screened, some representative up- and down-regulated genes were randomly sampled to verify the sequencing results by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Finally, functional annotations were completed, including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomic (KEGG) pathway analyses. The results showed that the sexual behavior of CSR rats did not change when compared with control group rats. The sperm concentration, viability and motility of the CSR rats decreased significantly, while the sperm malformation rate increased significantly. In the KEGG pathway analysis database, some specific differentially expressed genes were screened, which are involved in metabolic pathways, inflammation-related pathways, the renin-angiotensin system, etc. However, the aforesaid differentially expressed genes in the testes were not related to their DNA methylation status. CSR could significantly reduce the fertility of male rats, and one of its mechanisms occurs by altering gene expression in the testes, which has nothing to do with their DNA methylation. It was suggested that CSR could cause male infertility by significantly altering the testicular transcriptome.

Dataset Information

Chronic sleep restriction in the rotenone Parkinson's disease model in rats reveals peripheral early-phase biomarkers.

Publications

Chronic sleep restriction in the rotenone Parkinson's disease model in rats reveals peripheral early-phase biomarkers.

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