Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

Revuelta, Miren; Scheuer, Till; Chew, Li‐Jin; Schmitz, Thomas

doi:10.1007/s11064-020-02961-z

Cited by 11 publications

(8 citation statements)

References 134 publications

(164 reference statements)

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“…Importantly, microglial metabolism is closely linked to neuroinflammatory states [ 140 , 141 ], and both glucose and lipid metabolism regulate microglial activation [ 142 , 143 , 144 , 145 ]. The dysregulation of glial and microglial metabolism, proliferation and function can alter neuronal differentiation, impair synaptogenesis and pruning, and change neuroinflammatory states, with profound implications for neural architecture and connectivity [ 146 ].…”

Section: Discussionmentioning

confidence: 99%

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

Mahony

O’Ryan

2021

IJMS

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Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with extensive genetic and aetiological heterogeneity. While the underlying molecular mechanisms involved remain unclear, significant progress has been facilitated by recent advances in high-throughput transcriptomic, epigenomic and proteomic technologies. Here, we review recently published ASD proteomic data and compare proteomic functional enrichment signatures with those of transcriptomic and epigenomic data. We identify canonical pathways that are consistently implicated in ASD molecular data and find an enrichment of pathways involved in mitochondrial metabolism and neurogenesis. We identify a subset of differentially expressed proteins that are supported by ASD transcriptomic and DNA methylation data. Furthermore, these differentially expressed proteins are enriched for disease phenotype pathways associated with ASD aetiology. These proteins converge on protein–protein interaction networks that regulate cell proliferation and differentiation, metabolism, and inflammation, which demonstrates a link between canonical pathways, biological processes and the ASD phenotype. This review highlights how proteomics can uncover potential molecular mechanisms to explain a link between mitochondrial dysfunction and neurodevelopmental pathology.

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Section: Discussionmentioning

confidence: 99%

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

Mahony

O’Ryan

2021

IJMS

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“…Importantly, microglial metabolism is closely linked to neuroinflammatory state [141,142], and both glucose and lipid metabolism regulate microglial activation [143][144][145][146]. The dysregulation of glial and microglial metabolism, proliferation and function can alter neuronal differentiation, impair synaptogenesis and pruning, and change neuroinflammatory state, with profound implications for neural architecture and connectivity [147].…”

Section: Discussionmentioning

confidence: 99%

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

Mahony¹,

O’Ryan²

2021

Preprint

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Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with extensive genetic and aetiological heterogeneity. While the underlying molecular mechanisms involved remain unclear, significant progress has been facilitated by recent advances in high-throughput transcriptomic, epigenomic and proteomic technologies. Here, we review recently published ASD proteomic data and compare proteomic func-tional enrichment signatures to those of transcriptomic and epigenomic data. We iden-tify canonical pathways that are consistently implicated in ASD molecular data and find an enrichment of pathways involved in mitochondrial metabolism and neurogenesis. We identify a subset of differentially expressed proteins that are supported by ASD tran-scriptomic and DNA methylation data. Furthermore, these differentially expressed proteins are enriched for disease phenotype pathways associated with ASD aetiology. These proteins converge on protein-protein interaction networks that regulate cell pro-liferation and differentiation, metabolism and inflammation which demonstrates a link between canonical pathways, biological processes and the ASD phenotype. This review highlights how proteomics can uncover potential molecular mechanisms to explain a link between mitochondrial dysfunction and neurodevelopmental pathology.

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“…Studies of the cerebellum have extended its function of motor control to non-motor activities as well, including language, thought modulations, emotions and the ability to organize symbolic activities consecutively [23,24,25]. Moreover, inositol metabolism has been connected to both motor and non-motor functions of the cerebellum.…”

Section: Discussionmentioning

confidence: 99%

Expression of 1L-myo-Inositol -1-Phosphate Synthase (EC 5.5.1.4) is Deregulated in the Cerebellum of Curly Tail Mutant Mice

Alebous

Steele

Johnson

2020

JAMMR

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Previous research, defining spatial control of inositol phosphate biosynthesis in the developing brain of CBA (normal) and CT [curly tail (ct-CT) and straight tail (st-CT)] mutant mice implicated a role for 1l-myo-inositol 1-phosphate synthase (MIP) in normal functioning of the central nervous system. Biochemical research indicated that MIP enzymatic activity, conversion of glucose 6-phosphate into inositol phosphate, is highest in the cerebellum of ct-CT and lowest in st-CT, when compared to that of CBA mice. Here, we utilized microscopic and biochemical investigations to analyze and extend previous findings of MIP expression in the cerebellum. Results of this research indicated that MIP expression correlates, well, with its enzymatic activity in the cerebellum of CBA and CT mutant mice. Statistical analyses of fluorescent micrographs detected a significant difference in fluorescence intensity between MIP from ct-CT, st-CT, and CBA mice. These data support vital links between inositol phosphate biosynthesis, MIP expression, and normal functioning of the cerebellum. Moreover, published data, identifying significant behavioral differences in the CT mutant, as well as data linking motor and non-motor cerebellar functions to abnormal levels of inositol, support the conclusion that aspects of normal cerebellar functions require temporal and spatial control of inositol phosphate biosynthesis, MIP expression.

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Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

Cited by 11 publications

References 134 publications

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

Expression of 1L-myo-Inositol -1-Phosphate Synthase (EC 5.5.1.4) is Deregulated in the Cerebellum of Curly Tail Mutant Mice

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