MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome

Tai, Derek J.C.; Liu, Yen-Chen; Hsu, Wei‐Lun; Ma, Yun‐Li; Cheng, Sin Jhong; Liu, Shau Y.; Lee, Eminy H.Y.

doi:10.1038/ncomms10552

Cited by 60 publications

(77 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent study, we have found that IGF-1 and CRF both enhance the SUMOylation of MeCP2 that results in alleviation of Rett syndrome in Mecp2 conditional knockout mice. 57 The present result implicates that IGF-1 and CRF may also alleviate the pathology of AD through enhanced SUMOylation of HDAC1. But dexamethasone, a synthetic glucocorticoid that binds to the glucocorticoid receptor, did not affect HDAC1 SUMOylation.…”

Section: Discussionsupporting

confidence: 54%

“…25 For construction of the Myc-tagged sumo1 plasmid, the procedure used was the same as that described elsewhere. 57 For construction of the Flag-Mcl-1 plasmid, the procedure used was the same as that described previously. 13 For construction of the Flag-tagged Hdac1 - sumo1 fusion plasmid, the previously cloned Flag-tagged Hdac1 plasmid and Myc-tagged sumo1 plasmid were used as templates and the Hdac1 sequence was amplified with primers 5′-ATCGGGATCCATGGCGCAGACTCAGGGCA-3′ (forward) and 5′-ATCGGATATCGGCCATCTTGACCTCTTCT-3′ (reverse).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic regulation of HDAC1 SUMOylation as an endogenous neuroprotection against Aβ toxicity in a mouse model of Alzheimer’s disease

Tao

Hsu

et al. 2017

Cell Death Differ

View full text Add to dashboard Cite

Amyloid-β (Aβ) produces neurotoxicity in the brain and causes neuronal death, but the endogenous defense mechanism that is activated on Aβ insult is less well known. Here we found that acute Aβ increases the expression of PIAS1 and Mcl-1 via activation of MAPK/ERK, and Aβ induction of PIAS1 enhances HDAC1 SUMOylation in rat hippocampus. Knockdown of PIAS1 decreases endogenous HDAC1 SUMOylation and blocks Aβ induction of Mcl-1. Sumoylated HDAC1 reduces it association with CREB, increases CREB binding to the Mcl-1 promoter and mediates Aβ induction of Mcl-1 expression. Transduction of SUMO-modified lenti-HDAC1 vector to the hippocampus of APP/PS1 mice rescues spatial learning and memory deficit and long-term potentiation impairment in APP/PS1 mice. It also reduces the amount of amyloid plaque and the number of apoptotic cells in CA1 area of APP/PS1 mice. Meanwhile, HDAC1 SUMOylation decreases HDAC1 binding to the neprilysin promoter. These results together reveal an important role of HDAC1 SUMOylation as a naturally occurring defense mechanism protecting against Aβ toxicity and provide an alternative therapeutic strategy against AD. Cell Death and Differentiation (2017) 24, 597-614; doi:10.1038/cdd.2016.161; published online 10 February 2017The brain of Alzheimer's disease (AD) patient is characterized by the accumulation of senile plaques, and amyloid-β peptides (Aβ 1-40 and Aβ 1-42 ) are the major components of these senile plaques. Aβ is known to cause lipid peroxidation, free radical production, caspase 3 activation and DNA damage that eventually lead to neuronal death. [1][2][3] In addition, the Aβ peptide or overexpression of Aβ causes cognitive impairment in animals. 4,5 This cognitive impairment correlates with amyloid plaque formation 4,6 or precedes it. 7,8 Further, naturally secreted Aβ or the Aβ peptide also inhibits longterm potentiation (LTP) in the hippocampus in vivo and disrupts synaptic and network function. 9,10 More recently, we have found that Aβ induces the expression of activated signal transducer and activator of transcription-1 (STAT1) and Aβ induction of STAT1 mediates the memory-impairing effect of Aβ. 11 On the other hand, it is conceivable that when Aβ produces its toxicity, neurons would develop defense mechanisms to cope with Aβ toxicity. For example, a nonamyloidogenic neurotrophic peptide sAPPα is shown to activate neuroprotectin D1 and promote cell survival. 12 In addition, we have found that Aβ activates the MAPK/ERK-SGK (serum-and glucocorticoid-inducible kinase) signaling pathway for neuroprotection against Aβ insult. 13 However, with the role and mechanism of Aβ-induced toxicity been studied extensively, the endogenous protection mechanism induced by Aβ is less well known.Histone acetylation is one kind of epigenetic regulations that has an important role in a wide range of brain functions and disorders, and histone deacetylases (HDACs) regulate the homeostasis of histone acetylation. The HDAC family contains 18 HDAC proteins that belong to different classifications. Inhibitio...

show abstract

Section: Discussionsupporting

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Epigenetic regulation of HDAC1 SUMOylation as an endogenous neuroprotection against Aβ toxicity in a mouse model of Alzheimer’s disease

Tao

Hsu

et al. 2017

Cell Death Differ

View full text Add to dashboard Cite

show abstract

“…Although previous studies failed to demonstrate the genotype‐phenotype correlation regarding stereotypies [Carter et al, ; Temudo, ; Temudo et al, ], p.T158M, p.R168X, p.R270X, p.R106W, and p.R294X mutations were found to be associated with more types of stereotypies in this study. Some pathogenic mutations of MECP2 such as T158M may be associated with more severe phenotype as shown in previous studies [Tai et al, ]. In contrast, individuals with p.R106W, p.R168X, p.R306C, p.R255X, and C806del.G in this study were associated with more severe clinical severities and more advanced stages.…”

Section: Discussionmentioning

confidence: 67%

Variations of stereotypies in individuals with Rett syndrome: A nationwide cross‐sectional study in Taiwan

et al. 2017

View full text Add to dashboard Cite

Individuals with Rett syndrome (RTT) can have variable manifestations of stereotypies. In this nation-wide cross-sectional study, we recruited all individuals with RTT in Taiwan diagnosed as RTT by neurologists based on genetic findings and diagnostic criteria. The data were collected using questionnaire. A total 43 cases of typical RTT and 15 cases of atypical RTT, aged from 2.1 to 40.1 years, were enrolled. They included 3 (5.2%) in stage II, 42 (72.4%) in stage III, and 13 (22.4%) in stage IV. All individuals presented with at least one stereotypy. Individuals with atypical RTT had more varied stereotypies (mean: 14 ± 6) compared to those with typical RTT (mean: 9 ± 5) (P = 0.003). Flapping (73.3%) and wringing (58.1%) were the most common hand stereotypies in atypical and typical RTT, respectively. Compared with typical RTT, hair pulling, bruxism, retropulsion, and protrusion of lips were more common in atypical RTT (P = 0.003, P = 0.006, P = 0.003 and <0.001, respectively). The number of stereotypies did not differ among different stages, clinical severities, and hand functions. Although there were no age-related changes in stereotypies in atypical RTT, flapping (P = 0.012), clapping (P = 0.044), and mouthing with single hand (P = 0.009) were significantly more prevalent in individuals aged <10 years with typical RTT, and they decreased after 10 years. In conclusion, our study showed that the stereotypical movements varied in typical and atypical RTT, implying the heterogeneous nature of the disease and the pathogenic mechanisms of RTT with atypical features. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1204-1214. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

show abstract

“…The vast majority of humans with RTT are females with a heterozygous loss of function mutation who are therefore mosaic for the gene (Van den Veyver and Zoghbi, 2000). Mounting evidence from mice that carry mutations abolishing expression of MECP2 strongly suggests that it is an important regulator of plasticity in development and adulthood (Deng et al, 2010;McGraw et al, 2011;Noutel et al, 2011;Na et al, 2013;Deng et al, 2014;He et al, 2014;Krishnan et al, 2015;Tai et al, 2016;Krishnan et al, 2017;Gulmez Karaca et al, 2018). Nevertheless, little is known about how these mutations affect in vivo sensory responses and neurophysiological changes during behavioral learning and plasticity (Durand et al, 2012;Banerjee et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Maternal experience-dependent cortical plasticity in mice is circuit- and stimulus-specific and requires MECP2

Lau

Krishnan

Huang

et al. 2019

Preprint

View full text Add to dashboard Cite

The neurodevelopmental disorder Rett syndrome is caused by mutations in the gene Mecp2.Misexpression of the protein MECP2 is thought to contribute to neuropathology by causing dysregulation of plasticity. Female heterozygous Mecp2 mutants (Mecp2 het ) failed to acquire a learned maternal retrieval behavior when exposed to pups, an effect linked to disruption of parvalbumin-expressing inhibitory interneurons (PV+) in the auditory cortex. However, the consequences of dysregulated PV+ networks during early maternal experience for auditory cortical sensory activity are unknown. Here we show that maternal experience in wild-type adult female mice (Mecp2 wt ) triggers PV+-mediated disinhibition of auditory responses in deep-layer pyramidal neurons that is selective for behaviorally-relevant pup vocalizations. These neurons also exhibit sharpened tuning for pup vocalizations following maternal experience. All of these neuronal changes are abolished in Mecp2 het , suggesting that they are integral to maternal learning. Moreover, our data are consistent with a growing body of evidence that cortical networks are particularly vulnerable to mutations of Mecp2 in PV+ neurons.

show abstract

MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome

Cited by 60 publications

References 65 publications

Epigenetic regulation of HDAC1 SUMOylation as an endogenous neuroprotection against Aβ toxicity in a mouse model of Alzheimer’s disease

Epigenetic regulation of HDAC1 SUMOylation as an endogenous neuroprotection against Aβ toxicity in a mouse model of Alzheimer’s disease

Variations of stereotypies in individuals with Rett syndrome: A nationwide cross‐sectional study in Taiwan

Maternal experience-dependent cortical plasticity in mice is circuit- and stimulus-specific and requires MECP2

Contact Info

Product

Resources

About