Altered structural and functional connectivity in CSF1R-related leukoencephalopathy

Zhan, Feixia; Zhu, Zeyu; Liu, Qing; Zhou, Haiyan; Luan, Xinghua; Huang, Xiaojun; Liu, Xiaoli; Tian, Wen; Wang, Shi-Ge; Song, Xiaoxuan; Chen, Guang; Zhao, Ming-Liang; Wang, Ying; Tang, Huidong; Hu, Jiong; Chen, Shengdi; Li, Bin-Yin; Cao, Li

doi:10.1007/s11682-020-00360-0

Cited by 13 publications

(14 citation statements)

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“…The white matter lesion volume has been shown to be strongly correlated with mini‐mental state examination scores [29]. More detailed volumetric analysis has shown thalamic and hippocampal atrophy [30]. Multiparametric quantitative MRI has been applied with machine learning approaches to differentiate CSF1R ‐leukoencephalopathy from multiple sclerosis.…”

Section: Resultsmentioning

confidence: 99%

“…Several publications noted a decrease in N‐acetyl aspartate (nine cases) as well as an increase in choline and inositol (seven cases) and lactate (three cases). In one publication, more advanced diffusion kurtosis imaging was performed, which revealed diffusion abnormalities in the corpus callosum, periventricularly, deep white matter, subcortical U‐fibers, cortical midline structures, and deep grey matter structures [30]. Using resting‐state functional MRI, the same study demonstrated reduced functional connectivity between the caudate nuclei and the contralateral hippocampi [30].…”

Section: Resultsmentioning

confidence: 99%

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Neuroimaging phenotypes of CSF1R‐related leukoencephalopathy: Systematic review, meta‐analysis, and imaging recommendations

et al. 2021

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Neuroimaging phenotypes of CSF1R‐related leukoencephalopathy: Systematic review, meta‐analysis, and imaging recommendations

et al. 2021

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“…The primary function of the corpus callosum is to integrate the information by joining both cerebral hemispheres to process motor, sensory, and cognitive signals and disruption of myelination could potentially impact all these functions. Indeed, a study employing advanced MRI techniques revealed altered functional connectivity between the cerebral hemispheres in CRL patients and highlighted an association between their symptoms and the disconnection of the two cerebral hemispheres, due to the loss of connection fibers in the corpus callosum (40). Furthermore, studies in both autopsied tissue from CRL patients and the mouse model suggest that microglial activation contributes to the loss of callosal white matter (8, 10, 41, 42).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte Colony Stimulating Factor causes cerebellar deficits and anxiety in a mouse model of CSF-1 receptor-related leukoencephalopathy

Biundo

Chiţu

Tindi

et al. 2022

Preprint

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Colony stimulating factor (CSF) receptor-1 (CSF-1R)-related leukoencephalopathy (CRL) is an adult-onset, demyelinating neurodegenerative disease caused by autosomal dominant mutations in CSF1R, modeled by the Csf1r+/- mouse. The expression of Csf2, encoding granulocyte- macrophage CSF (GM-CSF) and of Csf3, encoding granulocyte CSF (G-CSF), are elevated in both mouse and human CRL brains. While monoallelic targeting of Csf2 has been shown to attenuate many behavioral and histological deficits of mouse CRL, including cognitive dysfunction and demyelination, the contribution of Csf3 has not been explored. In this manuscript, we investigate the behavioral, electrophysiological and histopathological phenotypes of CRL mice following monoallelic targeting of Csf3. We show that Csf3 heterozygosity normalized the Csf3 levels in Csf1r+/- mouse brains and ameliorated anxiety-like behavior, motor coordination and social interaction deficits, but not their cognitive impairment. Consistent with this, Csf3 heterozygosity attenuated microglial activation in the cerebellum and in the ventral but not in the dorsal hippocampus. Csf3 heterozygosity also failed to prevent demyelination. Csf1r+/- mice exhibited altered synaptic activity in the deep cerebellar nuclei (DCN) associated with increased deposition of the complement factor C1q on glutamatergic synapses and with increased engulfment of glutamatergic synapses by DCN microglia. These phenotypes were significantly ameliorated by monoallelic deletion of Csf3. Our findings indicate that G-CSF and GM-CSF play non-overlapping roles in mouse CRL development and suggest that G-CSF could be an additional therapeutic target in CRL.

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“…CD86 is involved in immune response as a proin ammatory cytokine (Chang et al 2020). Colony stimulating factor 1 receptor (CSF1R) can cause associated leukoencephalopathy (Zhan et al 2020) and neuroprotective effect of microglia cell depletion involved in PD and AD (Crapser et al 2020;Oh et al 2020). PPARG, CD86 and CSF1R were all involved in the proin ammatory process (Bancells et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Core Genes and Potential Drugs in Vestibular Schwannoma

Yan¹,

Liu²,

Huang³

et al. 2021

Preprint

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Vestibular schwannoma is a common intracranial benign tumor, but the current drug treatment effect is not obvious. Surgical treatment can usually lead to residual problems such as nerve damage. Therefore, there is no clear molecular target to facilitate better clinical treatment. We analyzed three microarray data sets (GSE39645, GSE54934 and GSE108524) derived from the Gene Expression Omnibus database (GEO). The GEO2R was used to screen for the differentially expressed genes (DEG) between vestibular schwannomas and normal tissues. The ontology function of genes and genome pathway enrichment analysis were performed using annotation, visualizative and comprehensive discovery databases to identify the pathways and functional annotation of DEGs. The protein-protein interactions of these DEGs were analyzed by searching the interaction gene database and visualized by Cytoscape software. The potential therapeutic drugs for vestibular schwannoma were searched by online gene drug interaction analysis.A total of 226 up-regulated and 148 down-regulated DEGs were identified. Among them, ten hub genes with high connectivity (EGFR, PPARG, CD86, CSF1R, SPP1, CDH2, CCND1, CAV1, CYBB and NCAM1) were selected as the central genes that may be closely related to the pathogenesis of vestibular schwannoma, which can be potential treatment targets of vestibular schwannoma. Afatinib and osimerinib may be potential therapeutic drugs.

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Altered structural and functional connectivity in CSF1R-related leukoencephalopathy

Cited by 13 publications

References 50 publications

Neuroimaging phenotypes of CSF1R‐related leukoencephalopathy: Systematic review, meta‐analysis, and imaging recommendations

Neuroimaging phenotypes of CSF1R‐related leukoencephalopathy: Systematic review, meta‐analysis, and imaging recommendations

Granulocyte Colony Stimulating Factor causes cerebellar deficits and anxiety in a mouse model of CSF-1 receptor-related leukoencephalopathy

Identification of Potential Core Genes and Potential Drugs in Vestibular Schwannoma

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