Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models

Deurloo, Marielle; Turlova, Ekaterina; Chen, Wen Liang; Lin, You Wei; Tam, Elaine; Tassew, Nardos G.; Wu, Mike; Huang, Ya-Chi; Crawley, Jacqueline N.; Monnier, Philippe P.; Groffen, Alexander J.; Sun, Hong; Osborne, Lucy R.; Zhang, Feng

doi:10.1007/s12035-018-1290-7

Cited by 18 publications

(9 citation statements)

References 31 publications

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“…Therefore, western blotting was performed on the first and seventh days after ORIF to evaluate the membrane expression of the GABA A R α1 subunit. Cadherin was used as positive control membrane marker (42,43). There was no difference in the expression of GABA A R α1 between Group C and Group IP 1 on day 1 (C vs. (Figure 3).…”

Section: Combinationmentioning

confidence: 92%

Combination of Isoflurane and Propofol as General Anesthesia During Orthopedic Surgery of Perioperative Cerebral Hypoperfusion Rats to Avoid Cognitive Impairment

Tang

Wang

et al. 2020

Front. Med.

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Background: Perioperative cerebral hypoperfusion (CH) is common, although the underlying mechanism of cognitive impairment that results due to perioperative cerebral hypoperfusion remains to be determined. Isoflurane anesthesia induces neuronal injury via endoplasmic reticulum (ER) stress, whereas a sub-anesthetic dose of propofol improves postoperative cognitive function. However, the effects of the combination of isoflurane plus propofol, which is a common aesthetic combination administered to patients, on ER stress and cognition remain unknown. Methods: We sought to determine the effects of isoflurane plus propofol on ER stress and cognitive function in rats insulted by cerebral hypoperfusion. Ligation of the bilateral common carotid arteries (CCA) was adopted to develop the cerebral hypoperfusion rat model. A second surgery, open reduction and internal fixation (ORIF), requiring general anesthesia, was performed 30 days later so that the effects of anesthetics on the cognitive function of CH rats could be assessed. Rats received isoflurane alone (1.9%), propofol alone (40 mg•kg −1 •h −1) or a combination of isoflurane and propofol (1% and 20 mg•kg −1 •h −1 or 1.4% and 10 mg•kg −1 •h −1). Behavioral studies (contextual fear conditioning [FC] test), histological analyses (Nissl staining) and biochemical analyses (western blotting of the harvested rat brain tissues) were employed. Results: Hippocampus-dependent memory of rats in group IP 1 (1% isoflurane plus 20 mg•kg −1 •h −1 propofol) was not impaired, and expression level of γ-aminobutyric acid A type receptor α1 subunit, a key cognition-related protein, remained normal. ER stress alleviator, binding immunoglobulin protein, increased extremely while ER stress transcription factor, C/EBP homologous protein, showed no statistical Bu et al. Anesthesia During Perioperative Cerebral Hypoperfusion difference compared with the control group. Numbers of surviving neurons confirmed the substantial neuronal damage caused by propofol or isoflurane alone. Conclusions: These data suggest that ER stress contributes to the underlying mechanism of cognitive impairment and that the combination of isoflurane and propofol did not aggravate cognitive impairment and ER stress in aging rats with CH that were further subjected to ORIF surgery.

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Section: Combinationmentioning

confidence: 92%

Combination of Isoflurane and Propofol as General Anesthesia During Orthopedic Surgery of Perioperative Cerebral Hypoperfusion Rats to Avoid Cognitive Impairment

Tang

Wang

et al. 2020

Front. Med.

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“…Finally, as another gene in the 7q11.23 Williams syndrome critical region, specifically the GTF2I gene, has also been linked to brain development and intellectual abilities (Morris et al, 2003;Ghaffari et al, 2018;Deurloo et al, 2019), we repeated our analyses in the general population samples with a SNP in the GTF2I gene previously associated with brain functioning, rs2527367 (Jabbi et al, 2015). This SNP is in high linkage disequilibrium with a number of other GTF2I SNPs between chromosomal location 73706683 and 73777987, and thus obviates the need to investigate a number of related GTF2I SNPs and minimizes the number of statistical procedures necessary (Jabbi et al, 2015).…”

Section: Sensitivity Analysesmentioning

confidence: 99%

Williams syndrome hemideletion and LIMK1 variation both affect dorsal stream functional connectivity

Gregory

Mervis

Elliott

et al. 2019

Brain

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“…Recent studies have also demonstrated that GTF2I is involved in neurodevelopment [33,34]. Importantly, the phenotype observed in mice mirrors that observed in humans [35].…”

Section: Spatiotemporal Network Identified Driver Gene and The Gtf2imentioning

confidence: 74%

Spatiotemporal 7q11.23 Protein Network Implicates the GTF2I-PRKDC-DDR Pathway During Early-Fetal Brain Development in Psychiatric Diseases

Lin

Chen

Wang

et al. 2020

Preprint

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Background: Recurrent deletions and duplications of chromosome 7q11.23 copy number variants (CNVs) are associated with several psychiatric disorders. Previous works showed GTF2I associated with Williams-Beuren syndrome, but pathways affected by GTF2I are poorly defined. Although phenotypic abnormalities have been observed in patients and animal models, the targeted human brain regions, developmental stages, protein networks, and signaling pathways, influenced by this CNV remain unclear. Results: Topological changes were observed in protein-protein interaction (PPI) networks throughout different stages of brain development. Early and late fetal periods of development in the cortex, striatum, hippocampus, and amygdale were observed as the vital periods and regions for 7q11.23 CNV proteins. As a driver gene, GTF2I interacted with PRKDC and BRCA1 to involve in DNA Damaging Response (DDR) pathway. The physical interaction between GTF2I with PRKDC was confirmed experimentally by the liquid chromatography-tandem mass spectrometry (LC-MS/MS). Conclusion: We identified that striatum, hippocampus, and amygdala are crucial regions for establishing connectivity between 7q11.23 proteins and their partners in early and late fetal periods. Our results suggested that GTF2I-PRKDC-DDR and GTF2I-BRCA1-DDR pathway is crucial for the 7q11.23 CNV genes to contribute to the pathogenesis of psychiatric diseases.

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Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models

Cited by 18 publications

References 31 publications

Combination of Isoflurane and Propofol as General Anesthesia During Orthopedic Surgery of Perioperative Cerebral Hypoperfusion Rats to Avoid Cognitive Impairment

Combination of Isoflurane and Propofol as General Anesthesia During Orthopedic Surgery of Perioperative Cerebral Hypoperfusion Rats to Avoid Cognitive Impairment

Williams syndrome hemideletion and LIMK1 variation both affect dorsal stream functional connectivity

Spatiotemporal 7q11.23 Protein Network Implicates the GTF2I-PRKDC-DDR Pathway During Early-Fetal Brain Development in Psychiatric Diseases

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