scholarly journals Intracerebroventricular Infusion of Gangliosides Augments the Adult Neural Stem Cell Pool in Mouse Brain

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141988485
Author(s):  
Yutaka Itokazu ◽  
Dongpei Li ◽  
Robert K. Yu
Keyword(s):  
Mouse Brain ◽  
Expression Profiles ◽  
Normal Brain ◽  
Behavioral Deficits ◽  
Adult Neural Stem Cell ◽  
Intracerebroventricular Infusion ◽  
5Xfad Mouse ◽  
Developing Mouse Brain ◽  
Ganglioside Gd3

We previously reported that ganglioside GD3 is the predominant species in neural stem cells (NSCs) and reduced postnatal NSC pools are observed in both the subventricular zone and dentate gyrus (DG) of GD3-synthase knockout (GD3S-KO) mouse brains. Specifically, deficiency of GD3 in GD3S-KO animals revealed a dramatic reduction in cellularity in the DG of the hippocampus of the developing mouse brain, resulting in severe behavioral deficits in these animals. To further evaluate the functional role of GD3 in postnatal brain, we performed rescue experiments by intracerebroventricular infusion of ganglioside GD3 in adult GD3S-KO animals and found that it could restore the NSC pools and enhance the NSCs for self-renewal. Furthermore, 5xFAD mouse model was utilized, and GD3 restored NSC numbers and GM1 promoted neuronal differentiation. Our results thus demonstrate that exogenously administered gangliosides are capable to restore the function of postnatal NSCs. Since ganglioside expression profiles are associated not only with normal brain development but also with pathogenic mechanisms of diseases, such as Alzheimer’s disease, we anticipate that the administration of exogenous gangliosides, such as GD3 and GM1, may represent a novel and effective strategy for promoting adult neurogenesis in damaged brain for disease treatment.

scholarly journals Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuen Gao ◽  
Natalia Duque-Wilckens ◽  
Mohammad B. Aljazi ◽  
Yan Wu ◽  
Adam J. Moeser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Molecular Mechanisms ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Normal Brain ◽  
Critical Function ◽  
Developmental Defects ◽  
Neurodevelopmental Disease ◽  
Developing Mouse Brain

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.

scholarly journals PDTM-09. Yap1 FUNCTION IN SEX-BIASED MEDULLOBLASTOMA FORMATION AND ANTI-TUMOR IMMUNITY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi188-vi188
Author(s):  
Nourhan Abdelfattah ◽  
Sivaraman Natarajan ◽  
Yaohui Chen ◽  
Kin-Hoe Chow ◽  
Shu-hsia Chen ◽  
...  
Keyword(s):  
Cytotoxic T Cells ◽  
Therapeutic Benefit ◽  
Tumor Formation ◽  
Normal Brain ◽  
A Cell ◽  
Developing Mouse Brain ◽  
Pediatric Brain ◽  
Normal Brain Development ◽  
Extended Survival

Abstract Immunotherapies offer remarkable potential to provide robust therapeutic benefit. Patients suffering from medulloblastoma (MB), the most frequent pediatric brain malignancy, can especially benefit from this approach, minimizing the devastating side effects of aggressive radiation and chemotherapies that disrupt normal brain development. However, regulators of the immune landscape remain poorly understood and no effective immunotherapies exist yet for MB. Here, we describe a sex-dependent Yap1 function in fSmoM2;GFAPcre SHH-MB (SG) mouse model. We show that Yap1 is both a cell-autonomous regulator of MB stem-cells and a non-cell-autonomous regulator of immune infiltrates in SHH-MB. Yap1 deletion in SG mice results in increased neuronal differentiation, significantly extended survival, and enhanced infiltration of peripheral blood immune cells (including cytotoxic T-cells, neutrophils, and macrophages). Additionally, this rescue phenotype is observed in a sex-biased manner: 65% of Yap1f/f;fSmoM2;GFAPcre males are rescued in contrast to 35% of females. These observations implicate Yap1 as a mediator of sex-biased brain-tumor formation, either through direct modulation of MB cells and/or through indirectly mediating the MB immune landscape. We are currently testing the role of sex-specific differences in the developing mouse brain to elucidate context-dependent function of Yap1 in MB genesis and maintenance.

scholarly journals Neurotoxic Effects of Fluorinated Glucocorticoid Preparations on the Developing Mouse Brain: Role of Preservatives

2001 ◽  
Vol 50 (6) ◽  
pp. 706-711 ◽  
Author(s):  
Olivier Baud ◽  
Vincent Laudenbach ◽  
Philippe Evrard ◽  
Pierre Gressens
Keyword(s):  
Mouse Brain ◽  
Neurotoxic Effects ◽  
Developing Mouse Brain

scholarly journals A Novel Method for the Simultaneous Enrichment, Identification, and Quantification of Phosphopeptides and Sialylated Glycopeptides Applied to a Temporal Profile of Mouse Brain Development

2012 ◽  
Vol 11 (11) ◽  
pp. 1191-1202 ◽  
Author(s):  
Giuseppe Palmisano ◽  
Benjamin L. Parker ◽  
Kasper Engholm-Keller ◽  
Sara Eun Lendal ◽  
Katarzyna Kulej ◽  
...  
Keyword(s):  
Brain Development ◽  
Mouse Brain ◽  
Dynamic Changes ◽  
Post Translational Modifications ◽  
Global View ◽  
Novel Method ◽  
Isobaric Tagging ◽  
Developing Mouse Brain ◽  
Mouse Brain Development

We describe a method that combines an optimized titanium dioxide protocol and hydrophilic interaction liquid chromatography to simultaneously enrich, identify and quantify phosphopeptides and formerly N-linked sialylated glycopeptides to monitor changes associated with cell signaling during mouse brain development. We initially applied the method to enriched membrane fractions from HeLa cells, which allowed the identification of 4468 unique phosphopeptides and 1809 formerly N-linked sialylated glycopeptides. We subsequently combined the method with isobaric tagging for relative quantification to compare changes in phosphopeptide and formerly N-linked sialylated glycopeptide abundance in the developing mouse brain. A total of 7682 unique phosphopeptide sequences and 3246 unique formerly sialylated glycopeptides were identified. Moreover 669 phosphopeptides and 300 formerly N-sialylated glycopeptides differentially regulated during mouse brain development were detected. This strategy allowed us to reveal extensive changes in post-translational modifications from postnatal mice from day 0 until maturity at day 80. The results of this study confirm the role of sialylation in organ development and provide the first extensive global view of dynamic changes between N-linked sialylation and phosphorylation.

scholarly journals Impaired KDM2B-mediated PRC1 recruitment to chromatin causes neural stem cell senescence and ASD/ID-like behavioral deficits

2021 ◽  
Author(s):  
Yuen Gao ◽  
Natalia Duque-Wilckens ◽  
Mohammad B Aljazi ◽  
Adam J Moeser ◽  
George I Mias ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Critical Role ◽  
Autism Spectrum ◽  
Normal Brain ◽  
Behavioral Deficits ◽  
Adult Mice ◽  
Cycle Arrest ◽  
Developing Mouse Brain ◽  
Underlying Mechanisms ◽  
Polycomb Repressive Complex 1

AbstractAutism spectrum disorder (ASD) and intellectual disability (ID) are neurodevelopmental diseases associated with various genetic mutations. Recent clinical studies report that chromosomal 12q24.31 microdeletions are associated with human ASD/ID. However, the causality and underlying mechanisms linking 12q24.31 microdeletions to ASD/ID pathogenesis remain undetermined. Here we show Kdm2b, one of the genes located in chromosomal 12q24.31, plays a critical role in maintaining neural stem cells (NSCs) in the developing mouse brain. Loss of the CxxC-ZF domain of KDM2B impairs its function in recruiting Polycomb repressive complex 1 (PRC1) to chromatin, resulting in de-repression of genes involved in cell apoptosis, cell cycle arrest, NSC premature senescence, and leading to the loss of NSC populations in the brain. Importantly, the Kdm2b mutation is sufficient to induce ASD/ID-like social and memory deficits in adult mice. Thus, our study reveals a critical role of an epigenetic factor KDM2B in normal brain development, a causality between the Kdm2b mutation and genesis of ASD/ID-like phenotypes in mice, and potential molecular mechanisms linking the function of KDM2B-PRC1 in transcriptional regulation and NSC senescence to the12q24.31 microdeletion-associated ASD/ID.

Author response for "Hemovasculogenic origin of blood vessels in the developing mouse brain"

2020 ◽  
Author(s):  
Miguel A. Gama Sosa ◽  
Rita De Gasperi ◽  
Gissel M. Perez ◽  
Patrick R. Hof ◽  
Gregory A. Elder
Keyword(s):  
Blood Vessels ◽  
Mouse Brain ◽  
Author Response ◽  
Developing Mouse Brain
Sign in / Sign up

Export Citation Format

Share Document