scholarly journals Experimental and computational analysis of calcium dynamics in 22q11.2 deletion model astrocytes

2021 ◽  
Author(s):  
Ivan V. Maly ◽  
Wilma A. Hofmann ◽  
Mikhail V. Pletnikov
Keyword(s):  
Intracellular Calcium ◽  
Molecular Mechanisms ◽  
Physiological State ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Calcium Dynamics ◽  
Imaging Data ◽  
22Q11.2 Deletion ◽  
Biological Time ◽  
Time Courses

ABSTRACTIntracellular calcium dynamics in spontaneously active cells such as neurons or astrocytes is an information-rich readout of the physiological state of the cell. Methods for deriving mechanistic information from biological time courses, as well as for extracting cellular activity time courses algorithmically from imaging data, have significantly advanced in recent years but been mostly applied to neuronal data. At the same time, the role of astrocytes, a type of glial brain cells, in enabling cognition and in psychiatric diseases is beginning to come into focus. In the present work, we analyze calcium dynamics in astrocytes from a transgenic mouse model of 22q11.2 deletion syndrome (DiGeorge syndrome), an inborn condition associated with psychiatric disorders and other abnormalities of development. Methods of calcium imaging, computer vision, and Bayesian inference are applied to compare normal and deletion-bearing cells. Inference of highest-likelihood molecular kinetic characteristics from the intracellular calcium time courses pinpoints a significant change in the activity of the sarcoendoplasmic reticulum calcium ATPase (SERCA). Applying a SERCA inhibitor to the normal cells reproduces the differences detected in the deletion-bearing cells. We conclude that Bayesian kinetic inference is a useful tool for mechanistic dissection of complex cellular phenotypes in neuropsychiatric glia research. Its application can allow rapid, rigorous formulation of specific hypotheses concerning the underlying molecular mechanisms, prioritization of experiments testing such hypotheses, and, in the future, individualized functional molecular diagnostics.

White matter abnormalities in 22q11.2 deletion syndrome patients showing cognitive decline

2017 ◽  
Vol 48 (10) ◽  
pp. 1655-1663 ◽  
Author(s):  
Jasper Olivier Nuninga ◽  
Marc Marijn Bohlken ◽  
Sanne Koops ◽  
Ania M. Fiksinski ◽  
René C. W. Mandl ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Internal Capsule ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Psychotic Episode ◽  
Imaging Data ◽  
22Q11.2 Deletion ◽  
White Matter Abnormalities ◽  
Cingulum Bundle

AbstractBackgroundDecline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.2 deletion syndrome (22q11DS) is an appealing model in this context, as 25% of patients develop psychosis. Furthermore, we recently showed that cognitive decline also precedes the onset of psychosis in individuals with 22q11DS. Here, we investigate whether the early cognitive decline in patients with 22q11DS is associated with alterations in white matter microstructure.MethodsWe compared the fractional anisotropy (FA) of white matter in 22q11DS patients with cognitive decline [n = 16; −18.34 (15.8) VIQ percentile points over 6.80 (2.39) years] to 22q11DS patients without cognitive decline [n = 18; 17.71 (20.17) VIQ percentile points over 5.27 (2.03) years] by applying an atlas-based approach to diffusion-weighted imaging data.ResultsFA was significantly increased (p < 0.05, FDR) in 22q11DS patients with a cognitive decline in the bilateral superior longitudinal fasciculus, the bilateral cingulum bundle, all subcomponents of the left internal capsule and the left superior frontal-occipital fasciculus as compared with 22q11DS patients without cognitive decline.ConclusionsWithin 22q11DS, the early cognitive decline is associated with microstructural differences in white matter. At the mean age of 17.8 years, these changes are reflected in increased FA in several tracts. We hypothesize that similar brain alterations associated with cognitive decline take place early in the trajectory of schizophrenia.

scholarly journals Investigation of Neurodevelopmental Deficits of 22 q11.2 Deletion Syndrome with a Patient-iPSC-Derived Blood–Brain Barrier Model

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2576
Author(s):  
Yunfei Li ◽  
Yifan Xia ◽  
Huixiang Zhu ◽  
Eric Luu ◽  
Guangyao Huang ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
22Q11.2 Deletion Syndrome ◽  
Cell Junctions ◽  
Brain Barrier ◽  
Endothelial Glycocalyx ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Solute Permeability ◽  
Blood Brain

The blood–brain barrier (BBB) is important in the normal functioning of the central nervous system. An altered BBB has been described in various neuropsychiatric disorders, including schizophrenia. However, the cellular and molecular mechanisms of such alterations remain unclear. Here, we investigate if BBB integrity is compromised in 22q11.2 deletion syndrome (also called DiGeorge syndrome), which is one of the validated genetic risk factors for schizophrenia. We utilized a set of human brain microvascular endothelial cells (HBMECs) derived from the induced pluripotent stem cell (iPSC) lines of patients with 22q11.2-deletion-syndrome-associated schizophrenia. We found that the solute permeability of the BBB formed from patient HBMECs increases by ~1.3–1.4-fold, while the trans-endothelial electrical resistance decreases to ~62% of the control values. Correspondingly, tight junction proteins and the endothelial glycocalyx that determine the integrity of the BBB are significantly disrupted. A transcriptome study also suggests that the transcriptional network related to the cell–cell junctions in the compromised BBB is substantially altered. An enrichment analysis further suggests that the genes within the altered gene expression network also contribute to neurodevelopmental disorders. Our findings suggest that neurovascular coupling can be targeted in developing novel therapeutical strategies for the treatment of 22q11.2 deletion syndrome.

Surgical Management of Patients With 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (5) ◽  
pp. 857-869
Author(s):  
Oksana A. Jackson ◽  
Alison E. Kaye
Keyword(s):  
Surgical Management ◽  
Preoperative Evaluation ◽  
Preoperative Assessment ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Surgical Decision ◽  
Obstructive Sleep ◽  
Spine Abnormalities ◽  
Speech Assessment

Purpose The purpose of this tutorial was to describe the surgical management of palate-related abnormalities associated with 22q11.2 deletion syndrome. Craniofacial differences in 22q11.2 deletion syndrome may include overt or occult clefting of the palate and/or lip along with oropharyngeal variances that may lead to velopharyngeal dysfunction. This chapter will describe these circumstances, including incidence, diagnosis, and indications for surgical intervention. Speech assessment and imaging of the velopharyngeal system will be discussed as it relates to preoperative evaluation and surgical decision making. Important for patients with 22q11.2 deletion syndrome is appropriate preoperative screening to assess for internal carotid artery positioning, cervical spine abnormalities, and obstructive sleep apnea. Timing of surgery as well as different techniques, common complications, and outcomes will also be discussed. Conclusion Management of velopharyngeal dysfunction in patients with 22q11.2 deletion syndrome is challenging and requires thoughtful preoperative assessment and planning as well as a careful surgical technique.

Psychosocial Risks and Management for Children and Adolescents With 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (4) ◽  
pp. 633-640 ◽  
Author(s):  
Canice E. Crerand ◽  
Ari N. Rabkin
Keyword(s):  
Cognitive Abilities ◽  
Psychotic Disorders ◽  
Developmental Stages ◽  
Early Adulthood ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Psychosocial Risks ◽  
Empirically Supported ◽  
Specific Education

Purpose This article reviews the psychosocial risks associated with 22q11.2 deletion syndrome, a relatively common genetic condition associated with a range of physical and psychiatric problems. Risks associated with developmental stages from infancy through adolescence and early adulthood are described, including developmental, learning, and intellectual disabilities as well as psychiatric disorders including anxiety, mood, and psychotic disorders. Other risks related to coping with health problems and related treatments are also detailed for both affected individuals and their families. Conclusion The article ends with strategies for addressing psychosocial risks including provision of condition-specific education, enhancement of social support, routine assessment of cognitive abilities, regular mental health screening, and referrals for empirically supported psychiatric and psychological treatments.

Conotruncal heart defects and aortic arch anomalies in fetuses with 22q11.2 deletion syndrome

2020 ◽  
Author(s):  
I.V. Novikova, O.M. Khurs, T.V. Demidovich et all
Keyword(s):  
Aortic Arch ◽  
Heart Defects ◽  
22Q11.2 Deletion Syndrome ◽  
Ventricular Outflow Tract ◽  
Double Outlet Right Ventricle ◽  
Interrupted Aortic Arch ◽  
Left Ventricular ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Aortic Arch Anomalies

16 second trimester fetuses with 22q11.2 deletion syndrome have been examined at anatomic-pathological investigation. Main cardiovascular diseases were ascending aorta hypoplasia with aortic valve stenosis (n = 6; 37.5%), truncus arteriosus (n = 5; 31.25%), tetralogy of Fallot (n = 3; 18.75%) and double-outlet right ventricle (n = 1; 6.25%). Ventricular septal defect was present in 16 cases. Associated aortic arch anomalies included interrupted aortic arch (n = 9; 56.25%), right aortic arch (n = 6; 37.5%), retroesophageal ring (n = 1; 6.25%) and aberrant right subclavian arteria (n = 5; 31.25%). 5 fetuses had left ventricular outflow tract obstructive lesions with interrupted aortic arch of type B combined with aberrant right subclavian arteria.

scholarly journals Toward co‐production of research in 22q11.2 deletion syndrome: Research needs from the caregiver's perspective

2020 ◽  
Vol 74 (11) ◽  
pp. 626-627
Author(s):  
Hidetaka Tamune ◽  
Yousuke Kumakura ◽  
Ryo Morishima ◽  
Akiko Kanehara ◽  
Miho Tanaka ◽  
...  
Keyword(s):  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Research Needs ◽  
22Q11.2 Deletion
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