Search results for "cortical development"
showing 10 items of 16 documents
Models for preterm cortical development using non invasive clinical EEG
2017
AbstractThe objective of this study was to evaluate the piglet and the mouse as model systems for preterm cortical development. According to the clinical context, we used non invasive EEG recordings. As a prerequisite, we developed miniaturized Ag/AgCl electrodes for full band EEG recordings in mice and verified that Urethane had no effect on EEG band power. Since mice are born with a “preterm” brain, we evaluated three age groups: P0/P1, P3/P4 and P13/P14. Our aim was to identify EEG patterns in the somatosensory cortex which are distinguishable between developmental stages and represent a physiologic brain development. In mice, we were able to find clear differences between age groups wit…
Characterization and Stage-Dependent Lineage Analysis of Intermediate Progenitors of Cortical GABAergic Interneurons
2021
Intermediate progenitors of both excitatory and inhibitory neurons, which can replenish neurons in the adult brain, were recently identified. However, the generation of intermediate progenitors of GABAergic inhibitory neurons (IPGNs) has not been studied in detail. Here, we characterized the spatiotemporal distribution of IPGNs in mouse cerebral cortex. IPGNs generated neurons during both embryonic and postnatal stages, but the embryonic IPGNs were more proliferative. Our lineage tracing analyses showed that the embryonically proliferating IPGNs tended to localize to the superficial layers rather than the deep cortical layers at 3 weeks after birth. We also found that embryonic IPGNs derive…
Broad neurodevelopmental features and cortical anomalies associated with a novel de novo KMT2A variant in Wiedemann-Steiner syndrome.
2021
Abstract Wiedemann-Steiner syndrome (WDSTS) is a rare genetic disorder including developmental delay/intellectual disability (DD/ID), hypertrichosis cubiti, short stature, and distinctive facial features, caused by mutation in KMT2A gene, which encodes a histone methyltransferase (H3K4) that regulates chromatin-mediated transcription. Different neurodevelopmental phenotypes have been described within the WDSTS spectrum, including a peculiar Autism Spectrum Disorder (ASDs) subtype in some affected individuals. Here, we report a 9-year-old Caucasian male found by next-generation panel sequencing to carry a novel heterozygous de novo KMT2A frameshift variant (NM_001197104.2:c.4433delG; p. Arg1…
Compassionate use of everolimus for refractory epilepsy in a patient with MTOR mosaic mutation
2020
Abstract The MTOR gene encodes the mechanistic target of rapamycin (mTOR), which is a core component of the PI3K-AKT-mTOR signaling pathway. Postzygotic MTOR variants result in various mosaic phenotypes, referred to in OMIM as Smith-Kinsgmore syndrome or focal cortical dysplasia. We report here the case of a patient, with an MTOR mosaic gain-of-function variant (p.Glu2419Lys) in the DNA of 41% skin cells, who received compassionate off-label treatment with everolimus for refractory epilepsy. This 12-year-old-girl presented with psychomotor regression, intractable seizures, hypopigmentation along Blaschko's lines (hypomelanosis of Ito), asymmetric regional body overgrowth, and ocular anomali…
Models of cortical malformation--Chemical and physical.
2015
Abstract Pharmaco-resistant epilepsies, and also some neuropsychiatric disorders, are often associated with malformations in hippocampal and neocortical structures. The mechanisms leading to these cortical malformations causing an imbalance between the excitatory and inhibitory system are largely unknown. Animal models using chemical or physical manipulations reproduce different human pathologies by interfering with cell generation and neuronal migration. The model of in utero injection of methylazoxymethanol (MAM) acetate mimics periventricular nodular heterotopia. The freeze lesion model reproduces (poly)microgyria, focal heterotopia and schizencephaly. The in utero irradiation model caus…
Transient hypothyroidism during lactation alters the development of the corpus callosum in rats. An in vivo magnetic resonance image and electron mic…
2020
Magnetic resonance imaging (MRI) data of children with late diagnosed congenital hypothyroidism and cognitive alterations such as abnormal verbal memory processing suggest altered telencephalic commissural connections. The corpus callosum (CC) is the major inter-hemispheric commissure that contra-laterally connects neocortical areas. However, in late diagnosed neonates with congenital hypothyroidism, the possible effect of early transient and chronic postnatal hypothyroidism still remains unknown. We have studied the development of the anterior, middle and posterior CC, using in vivo MRI and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI) treated r…
Both rare and de novo copy number variants are prevalent in agenesis of the corpus callosum but not in cerebellar hypoplasia or polymicrogyria.
2013
Agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and polymicrogyria (PMG) are severe congenital brain malformations with largely undiscovered causes. We conducted a large-scale chromosomal copy number variation (CNV) discovery effort in 255 ACC, 220 CBLH, and 147 PMG patients, and 2,349 controls. Compared to controls, significantly more ACC, but unexpectedly not CBLH or PMG patients, had rare genic CNVs over one megabase (p = 1.48×10−3; odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.89–5.39). Rare genic CNVs were those that impacted at least one gene in less than 1% of the combined population of patients and controls. Compared to controls, significantly more AC…
3T Double Inversion Recovery Magnetic Resonance Imaging: diagnostic advantages in the evaluation of cortical development anomalies
2016
Abstract Purpose The aim of this work was to investigate the diagnostic value of the DIR sequence at 3T MR imaging operating in the evaluation of cortical development anomalies. Methods We studied 40 patients, with a previous diagnosis of cortical dysplasia, by FLAIR-3D, DIR, FSE T2 and MPR-GE T1 sequences at 3T MRI. Two independent observers evaluated, for each sequence and lesion, some semiological aspects (cortical thickness, cortical signal intensity, white-gray matter blurring, subcortical white matter intensity). We made also a quantitative evaluation of the cortical signal intensity in lesion site, drawing a ROI on each MRI sequences and comparing them to the correspondent normal con…
Differential expression levels of Sox9 in early neocortical radial glial cells regulate the decision between stem cell maintenance and differentiation
2021
ABSTRACTRadial glial progenitor cells (RGCs) in the dorsal forebrain directly or indirectly produce excitatory projection neurons and macroglia of the neocortex. Recent evidence shows that the pool of RGCs is more heterogeneous than originally thought and that progenitor subpopulations can generate particular neuronal cell types. Using single cell RNA sequencing, we have studied gene expression patterns of two subtypes of RGCs that differ in their neurogenic behavior. One progenitor type rapidly produces postmitotic neurons, whereas the second progenitor remains relatively quiescence before generating neurons. We have identified candidate genes that are differentially expressed between thes…
Spontaneous Epileptic Manifestations in a DCX Knockdown Model of Human Double Cortex
2010
Previous reports indicate that in utero knockdown of doublecortin (DCX) results in the genesis of a subcortical heterotopia reminiscent of the doublecortex observed in female patients with DCX mutations. It has also been shown that these rats display an increased susceptibility to convulsant agents and increased cortical neurons excitability; but it is presently unknown whether they display spontaneous seizures. Furthermore, the link between the size of heterotopia and the clinical manifestation remained to be elucidated. Using video--electrocorticogram recordings, we now report that DCX knockdown induces frequent spontaneous seizures commonly associated with myoclonic jerks in adult rats. …