Collapse of complexity of brain and body activity due to excessive inhibition and MeCP2 disruption

Li, Jingwen; Kells, Patrick A.; Osgood, Ayla C; Gautam, Shree Hari; Shew, Woodrow L.

doi:10.1073/pnas.2106378118

Cited by 10 publications

(7 citation statements)

References 53 publications

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“…The motor cortex encodes the motor-related neural signals via coordinated activities among particular neural populations ( Jackson et al, 2003 ; Torre et al, 2016 ). Emerging evidence based on rat models of Rett syndrome has shown that MeCP2 disruption induced imbalanced inhibition of the motor cortex ( Li et al, 2021 ), suggesting the role of MeCP2 level on coordinated functional activities in the motor cortex. Furthermore, S1 has rich fiber pathways interconnected with the motor cortex, and interactions between the S1 and motor cortex underpin accurate movement control ( Borich et al, 2015 ; Perruchoud et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Aberrant brain functional and structural developments in MECP2 duplication rats

Calhoun

et al. 2022

Neurobiology of Disease

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Section: Discussionmentioning

confidence: 99%

Aberrant brain functional and structural developments in MECP2 duplication rats

Calhoun

et al. 2022

Neurobiology of Disease

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“…Limb associated motor dysfunctions may be under greater influence by corticospinal pathways than those of respiratory or respiratory associated motor dysfunctions [ 10 ] ( Figure 1 ). Excessive inhibition in the motor cortex in MECP2 models [ 216 , 227 , 228 ] is not found in patients, which exhibit cortical hyperexcitability [ 229 , 230 ]. Despite there being difficulties in localizing specific pathophysiologies of motor stereotypies, reduced GABA in cingulate and striatal regions were associated with a patient population with complex motor stereotypies [ 231 ].…”

Section: Inhibitory Influences On Rett Syndromementioning

confidence: 99%

Inhibitory Synaptic Influences on Developmental Motor Disorders

Fogarty

2023

IJMS

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During development, GABA and glycine play major trophic and synaptic roles in the establishment of the neuromotor system. In this review, we summarise the formation, function and maturation of GABAergic and glycinergic synapses within neuromotor circuits during development. We take special care to discuss the differences in limb and respiratory neuromotor control. We then investigate the influences that GABAergic and glycinergic neurotransmission has on two major developmental neuromotor disorders: Rett syndrome and spastic cerebral palsy. We present these two syndromes in order to contrast the approaches to disease mechanism and therapy. While both conditions have motor dysfunctions at their core, one condition Rett syndrome, despite having myriad symptoms, has scientists focused on the breathing abnormalities and their alleviation—to great clinical advances. By contrast, cerebral palsy remains a scientific quagmire or poor definitions, no widely adopted model and a lack of therapeutic focus. We conclude that the sheer abundance of diversity of inhibitory neurotransmitter targets should provide hope for intractable conditions, particularly those that exhibit broad spectra of dysfunction—such as spastic cerebral palsy and Rett syndrome.

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“…Rett syndrome (RTT), another neurodevelopmental disorder, which almost exclusively affects girls and appears after 6 months of age, is epitomized by repetitive body movements, difficulty with chewing, and poor intellectual abilities. At the molecular level, the disorder is characterized by the decline of the MECP2 levels that, according to Li et al., leads to “excessive synchrony and a collapse of complexity in the relationships among cortical neurons and the relationships between neurons and the body.” 278 Neuronal stimulation leads to elevated seizure susceptibility in RTT mice, 217 and neurally induced gene splicing is also observed in glia cells 233 and peripheral tissues 279 …”

Section: Alternative Splicing Of Mrnamentioning

confidence: 99%

On the origin and nature of nongenetic information in eumetazoans

Cabej

2023

Annals of the New York Academy of Sciences

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Nongenetic information implies all the forms of biological information not related to genes and DNA in general. Despite the deep scientific relevance of the concept, we currently lack reliable knowledge about its carriers and origins; hence, we still do not understand its true nature. Given that genes are the targets of nongenetic information, it appears that a parsimonious approach to find the ultimate source of that information is to trace back the sequential steps of the causal chain upstream of the target genes up to the ultimate link as the source of the nongenetic information. From this perspective, I examine seven nongenetically determined phenomena: placement of locus‐specific epigenetic marks on DNA and histones, changes in snRNA expression patterns, neural induction of gene expression, site‐specific alternative gene splicing, predator‐induced morphological changes, and cultural inheritance. Based on the available evidence, I propose a general model of the common neural origin of all these forms of nongenetic information in eumetazoans.

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Collapse of complexity of brain and body activity due to excessive inhibition and MeCP2 disruption

Cited by 10 publications

References 53 publications

Aberrant brain functional and structural developments in MECP2 duplication rats

Aberrant brain functional and structural developments in MECP2 duplication rats

Inhibitory Synaptic Influences on Developmental Motor Disorders

On the origin and nature of nongenetic information in eumetazoans

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