BTBD9 and dopaminergic dysfunction in the pathogenesis of restless legs syndrome

Lyu, Shangru; Doroodchi, Atbin; Xiao, Hong; Sheng, Yi; DeAndrade, Mark P.; Yang, Youfeng; Johnson, Tracy; Clemens, Stefan; Yokoi, Fumiaki; Miller, Michael A.; Xiao, Rui; Li, Yuqing

doi:10.1007/s00429-020-02090-x

Cited by 15 publications

(19 citation statements)

References 76 publications

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“…Future studies will define the role of medium spiny neurons and the interaction of striatal dopaminergic and cholinergic systems. These can be accomplished by selective knockout of Meis1 in the medium spiny neurons, and in dopaminergic or cholinergic neurons (Lyu, Doroodchi, Xing, et al, 2020; Lyu, Xing, et al, 2019). These efforts will promote the development of highly selective anti‐RLS drugs with fewer side effects.…”

Section: Discussionmentioning

confidence: 99%

“…Worms were mounted on a 1% agarose pad and images captured by a CCD camera (Qimaging optiMOS, Catalog #: 01‐OPTIMOS‐R‐M‐16‐C, year of purchase, 2017) on an Olympus BX51 microscope at 10 × (for representative figures) and 40 × (for quantification) magnifications. Fluorescence intensity was measured in mean gray value using ImageJ, with backgrounds subtracted with a rolling ball radius of 200 pixels (Lyu, Doroodchi, Xing, et al, 2020; Thompson et al., 2014). GFP was measured from the circled head region.…”

Section: Methodsmentioning

confidence: 99%

“…The experiment was performed as described (Lyu, DeAndrade, et al, 2019, 2020; Lyu, Doroodchi, Sheng, et al, 2020; Lyu, Doroodchi, Xing, et al, 2020). The sample size was determined according to (Lyu et al, 2019; Lyu, DeAndrade, et al, 2020; Lyu, Doroodchi, Sheng, et al, 2020; Lyu, Doroodchi, Xing, et al, 2020). The striata were dissected at 10:00 a.m. from 7 Meis1 KO males and 7 WT males with the average age of 6 months to measure TH, choline acetyltransferase (ChAT), acetylcholinesterase (AChE), choline transporter (ChT), and vesicular acetylcholine transporter (VAChT).…”

Section: Methodsmentioning

confidence: 99%

“…Each mouse was tested three times. Thirty‐one Meis1 KO males and 28 WT males with an average age of 5 months were used in the tail‐flick test (Lyu, Doroodchi, Sheng, et al, 2020; Lyu, Doroodchi, Xing, et al, 2020; Lyu, Xing, DeAndrade, Perez, Yokoi, et al, 2020; Lyu, Xing, DeAndrade, Perez, Zhang, et al, 2020). The sample size was determined according to (Sora et al., 1997).…”

Section: Methodsmentioning

confidence: 99%

“…The experiment was performed as described Lyu, Doroodchi, Xing, et al, 2020). The sample size was determined according to Lyu, Doroodchi, Xing, et al, 2020).…”

Section: Western Blotmentioning

confidence: 99%

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Deficiency of Meis1, a transcriptional regulator, in mice and worms: Neurochemical and behavioral characterizations with implications in the restless legs syndrome

Lyu

Xiao

Liu

et al. 2020

Journal of Neurochemistry

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Restless legs syndrome is a sleep-related sensorimotor neurological disease affecting up to 10% of the population. Genetic analyses have identified Myeloid Ecotropic viral Integration Site 1 (MEIS1), a transcriptional regulator, to be associated with not only the restless legs syndrome but also self-reported symptoms of insomnia and sleep. This study is to determine if Meis1 deficiency in mice can lead to restless legs syndrome-like phenotypes, and if it is the case, what the underlying mechanisms are. We used two genetic model systems, Caenorhabditis elegans and mice. Egg retention assay and fluorescent reporters were used with C. elegans. For mice, we performed behavioral tests, serum and brain iron detection, qRT-PCR, western blot, immunohistochemistry, and in vitro brain-slice recording. Our results showed that with C. elegans, the function of dop-3, an orthologue of DRD2, was diminished after the knockdown of unc-62, an ortholog of MEIS1. Additionally, unc-62 knockdown led to enhanced transcription of the orthologue of tyrosine hydroxylase, cat-2. Meis1 knockout mice were hyperactive and had a rest-phase-specific increased probability of waking. Moreover, Meis1 knockout mice had increased serum ferritin and altered striatal dopaminergic and cholinergic systems. Specifically, Meis1 knockout mice showed an increased mRNA level but decreased protein level of tyrosine hydroxylase in the striatum. Furthermore, Meis1 knockout mice had increased striatal dopamine turnover and decreased spontaneous firing regularity of striatal cholinergic interneurons. Our data suggest that Meis1 knockout mice have restless legs syndrome-like motor restlessness and changes in serum ferritin levels. The symptoms may be related to dysfunctional dopaminergic and cholinergic systems.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The experiment was performed as described Lyu, Doroodchi, Xing, et al, 2020). The sample size was determined according to Lyu, Doroodchi, Xing, et al, 2020).…”

Section: Western Blotmentioning

confidence: 99%

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