Table 1.
Altered circadian rhythm genes in animal models and patients with Parkinson's disease.
| PD models | Samples | Methods | Results and conclusions | References |
|---|---|---|---|---|
| Rats induced by 6-OHDA | Striatum | RT-qPCR; WB | Bmal1, Per2↓, Rorα↑. A link between attenuated antioxidative response and circadian dysregulations in PD. | Wang et al. [101] |
| Rats induced by 6-OHDA treated with levodopa | Striatum, SCN, Plasma | RT- qPCR; ELISA; HPLC | After levodopa treatment, Bmal1↓, peak of Per2 delayed, cortisol secretion↑, melatonin↓ | Li et al. [163] |
| RIPD rats | Substantia nigra | RT-qPCR; WB | Bmal1, Clock, NPAS2, Per1 and Per2, Rev-erbα and DBP↓. Chronic low-grade neuroinflammation aggravates circadian dysregulation in RIPD rats. | Li et al. [110] |
| Mul1A6 and park1 mutants Drosophila | Brain | RT-qPCR; IHC; WB | Mul1 and park mutations disrupt Per, Tim, and Clock normal circadian rhythmic expression during the day. ATG5↓, autophagy involved in circadian dysregulation | Doktór et al. [27] |
| MPTP mouse | SCN | Bioluminescence, RT-PCR | Bmal1, Cry1, Rev-erbα↓, activation of AMPK causes circadian dysfunction | Hayashi et al. [152] |
| Rats injected with Mn2+ | Hypothalamus | RT-qPCR; IHC | Bmal1, Clock, NPAS2, Cry1, Per1 and Per2↓, Nr1d1 and DBP↑. Mn2+ administration produces abnormal circadian rhythm gene expression | Li et al. [102] |
| ASO transgenic mice | SCN | IHC | Per2 expression is not altered in the SCN of ASO mice, weakening of circadian output is a core feature of PD | Kudo et al. [99] |
| 17 PD patients | PBL | RT-qPCR | Bmal1, Bmal2↓.The relative Bmal1 level correlates positively with PD severity |
Cai et al. [132] Ding et al. [133] |
| 239 PD patients | PBL | ELISA, RT-qPCR | Serum cortisol level↑, circulating melatonin level↓ | Breen et al. [6] |
| 206 PD patients | PBL | MSP and sequencing | Methylation only detected in the CRY1 and NPAS2 promoters. NPAS2 hypomethylation detected in PD vs control | Lin et al. [134] |
| 480 PD patients | PBL | PCR-RFLP | Polymorphism of Tef rs738499 is associated with depression symptoms in PD | Hua et al. [57] |
| 1394 PD patients | PBL | Illumina GoldenGate chips | Genetic polymorphisms in Bmal1 and Per1genes contribute to PD | Gu et al. [136] |
| 646 PD patients | PBL | Competitive allele-specific PCR | CLOCK 3111T/C variant can be an independent risk factor for motor fluctuation and sleep disorders in PD | Lou et al. [138] |
The animal models of PD as well as the number of patients with PD, the tissues, methods of examination, and the conclusions in each study are displayed