Disorder Of Neural Development Research Articles

16p11.2 is required for neuronal polarity

Since Autism Spectrum Disorder (ASD) is strongly associated with chromosomal abnormalities of 16p11.2, and Autism has been linked to neuronal polarity defect, our study aimed to explore the role of 16p11.2 genes in regulating neuronal polarity. We performed a neuronal polarity assay in a high throughput manner for candidate genes at 16p11.2. Our most interesting finding was that three 16p11.2 candidate genes, DOC2a, Tbx-6 and KIF 22, affected neuronal polarity. Our research, for the first time, indicates a novel association between 16p11.2 and neuronal polarity. Our results support the hypothesis that 16p11.2 is required for neuronal polarity. Our research provides new important insights into molecular mechanisms underlying the tight association between 16p11.2 and several neural developmental disorders, including autism, epilepsy, mental retardation and schizophrenia.

Addressing sleep disorder of autistic children with Qur’anic sound therapy

Autism is a neural development disorder characterized by the deterioration in social interacttion, abnormal language expression, repetitive actions, imaginative game tendencies, and limited and/or obsessiveness in certain activities/ interests. Lack of sleep is one of the factors contributing to the worsening of overall negative symptoms of autistic children. From the Islamic perspective, sleep is a necessity and could function as a treatment for health problems, in addition to influencing behavior patterns. Sound therapy has been used in dealing with various health problems, including sleep problems and mental ill health. Possibly, it can also address sleep problems of the autistic children. Listening to the melodious Qur’anic recitation is known to have therapeutic effects even on individuals who do not understand the meaning of the verses being read; it could function as sound therapy. However, no established work has been done to study the effect of Qur’anic verses recitation on autistic children and their sleep problems. Similar to the use of music therapy, Qur’anic recitation is also expected to have a positive impact on speech, learning and interpersonal relationship. As a healing medium, Qur’anic therapy is also expected to have a better result as compared to other conventional sound therapy since its content could be psychotherapeutic.

Neuroprotection of VEGF-expression neural stem cells in neonatal cerebral palsy rats

Cerebral palsy (CP) is a very common neural system development disorder that can cause physical disability in human. Here, we studied the neuroprotective effect of vascular endothelial growth factor (VEGF)-transfected neural stem cells (NSCs) in newborn rats with cerebral palsy (CP). Seven-day-old Sprague-Dawley rats were randomly divided into four groups: sham operation (control group), PBS transplantation (PBS group), VEGF+NSCs transplantation (transgene NSCs group) and NSCs transplantation groups (NSCs group). PBS, Transgene NSCs and NSCs groups respectively received stereotactic injections of PBS, lentiviral vector (pGC-FU-VEGF) infected NSCs or a NSCs suspension in the left sensory-motor cortex 3 days after CP model was established. The NSCs activity, their impacts on neural cell growth and apoptosis, brain development and animal behaviors were examined on the animals up to age 35-days. As expected, unilateral carotid artery occlusion plus hypoxia (cerebral palsy model) resulted in severe neural developmental disorders, including slowed growth, increased in cortical neuron apoptosis, decreased cerebral cortex micro-vessel density and retarded behavior developments. Transplantation of NSCs not only resulted in increases in VEGF protein expression in rat brains, but also largely prevented the behavioral defects and brain tissue pathology that resulted from cerebral palsy procedure, with animals received VEGF transfected NSCs always being marginally better than these received un-transfected cells. In conclusion, NSCs transplantation can partially prevent/slow down the brain damages that are associated with CP in the newborn rats, suggesting a new possible strategy for CP treatment.

A Gaming Model for Teaching Autistic Children Basic Traffic Rules

Autism is a disorder of neural development which affects about one in every 150 kids on average. Autism deals with major complexities regarding social communication and retention power. Now days, due to the increased use of the computer, the technology is being used to assist the treatment and to interact with an autistic child. To make the learning environment more attractive, the animated pictures are used in the applications. In this paper a gaming model is proposed which will first teach basic traffic rules to Autistic children with the help of some animated videos and then help them decide what action must be taken in certain situations thus increasing their intelligibility. The use of tangible objects is introduced so as to keep the sessions more interesting for autistic children.

The little molecules that could: a story about microRNAs in neural stem cells and neurogenesis

EDITORIAL article Front. Neurosci., 07 December 2012Sec. Neurogenesis Volume 6 - 2012 | https://doi.org/10.3389/fnins.2012.00176

ASPM regulates Wnt signaling pathway activity in the developing brain

Autosomal recessive primary microcephaly (MCPH) is a neural developmental disorder in which patients display significantly reduced brain size. Mutations in Abnormal Spindle Microcephaly (ASPM) are the most common cause of MCPH. Here, we investigate the underlying functions of Aspm in brain development and find that Aspm expression is critical for proper neurogenesis and neuronal migration. The Wnt signaling pathway is known for its roles in embryogenesis, and genome-wide siRNA screens indicate that ASPM is a positive regulator of Wnt signaling. We demonstrate that knockdown of Aspm results in decreased Wnt-mediated transcription, and that expression of stabilized β-catenin can rescue this deficit. Finally, coexpression of stabilized β-catenin can rescue defects observed upon in vivo knockdown of Aspm. Our findings provide an impetus to further explore Aspm's role in facilitating Wnt-mediated neurogenesis programs, which may contribute to psychiatric illness etiology when perturbed.

Does the "Dynamic Core" Approach Help to Manage Autistic Behavioral Disorders?

Back to table of contents Previous article Next article LettersFull AccessDoes the “Dynamic Core” Approach Help to Manage Autistic Behavioral Disorders?Fatemeh Bakouie, Shahriar Gharibzadeh, and Farzad TowhidkhahFatemeh BakouieSearch for more papers by this author, Shahriar GharibzadehSearch for more papers by this author, and Farzad TowhidkhahSearch for more papers by this authorPublished Online:1 Jul 2011https://doi.org/10.1176/jnp.23.3.jnpe1AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Autism is a neural development disorder in which some aspects of cognition, perception, and information-processing are disturbed. It seems that autistic patients have difficulties with processing complex situations. For example: 1) one main problem of autistic patients is their problematic involvement in social interactions, which are simply the hardest thing our brains have to process;1 2) motion sensitivity of autistic patients is significantly decreased for second-order (texture-defined) stimuli;2 3) auditory tests show that spectrally- and temporally dynamic tasks involving complex operations (evaluation, attention) are not performed appropriately in autistic persons.3 We suggest that the abovementioned autistic behaviors may be interpreted by the dynamic core hypothesis (DCH) of consciousness. According to the DCH, consciousness arises from a group of neurons (the dynamic core), whose dynamics are simultaneously differentiated and integrated. Based on this view, in conscious states, the dynamic core integrates different pieces of input information that have high entropy and variability, leading to conscious perception of these complex inputs.4 We suppose that ineffective dealing with complex stimuli in autistic patients may be the result of complexity-reduction in the dynamic core, which, in turn, leads to narrowing of consciousness. The cause of dynamic core complexity-reduction in autism may be related to some neurological findings: 1) some researchers suggest that atypical neural connectivity may lead to disturbed visual information-processing in autism;2 and 2) The gray matter in the brain of autistic patients is locally decreased in the mirror-neuron system (MNS) areas. MNS is supposed to be the basis of empathic behavior, which has a key role in social interactions. Moreover, cortical thinning of MNS in areas involved in emotion and social behavior was correlated with autism severity.5 We believe that behavioral treatment may help to repair the dynamic core defect in autistic patients. We propose that interacting with complex inputs at different levels of complexity must be taught to autistic patients. In accordance with our idea, some researchers have found that proper reward can increase response variability in autistic patients.6 This finding is a clue to increasing complex behaviors in autism as a result of proper training strategy. Meanwhile, newer studies in autism claim that “many educational approaches to autism have proceeded without a clear theoretical rationale.”7 We believe that using a DCH approach to managing autistic patients may be a beginning for dealing with this challenge.Neuromuscular Systems Laboratory, Biomedical Engineering Faculty, Amirkabir University of TechnologyCorrespondence: Shahriar Gharibzadeh, Neuromuscular Systems Laboratory, Biomedical Engineering Faculty, Amirkabir University of Technology, Somayyeh, Hafez, Tehran, Iran e-mail: [email protected]ac.ir1. Happé F , Ronald A , Plomin R : Time to give up on a single explanation for autism. Nature Neurosci 2006; 9:1218–1220Crossref, Medline, Google Scholar2. Bertone A , Mottron L , Jelenic P , et al.: Enhanced and diminished visuo-spatial information-processing in autism depends on stimulus complexity. Brain 2005; 128:2430–2441Crossref, Medline, Google Scholar3. Samson F , Mottron L , Jemel B , et al.: Can spectro-temporal complexity explain the autistic pattern of performance on auditory tasks? J Autism Dev Disord 2006, 36:65–76Crossref, Medline, Google Scholar4. Tononi GM , Edelman G , Sporns O : Complexity and coherency: integrating information in the brain. Trends Cogn Sci 1998; 2:474–484Crossref, Medline, Google Scholar5. Hadjikhani NM , Joseph R , Snyder J , et al.: Anatomical differences in the mirror neuron system and social cognition network in autism. Cerebral Cortex 2006; 16:1276–1282Crossref, Medline, Google Scholar6. Miller N , Neuringer A : Reinforcing variability in adolescents with autism. J Appl Behav Anal 2000; 33:151–165Crossref, Medline, Google Scholar7. Baron-Cohen S : The empathising-systemising theory of autism: implications for education. Tizard Learning Disability Review 2009; 4–13Crossref, Google Scholar FiguresReferencesCited byDetailsCited byNone Volume 23Issue 3 Summer 2011Pages E1-E1 Metrics PDF download History Published online 1 July 2011 Published in print 1 July 2011

O4-1.1 Neonatal conditions and autism spectrum disorders

BackgroundAutism spectrum disorders (ASDs) are disorders of neural development characterised by impaired social interaction and communication, and by restricted and repetitive behaviour. Only few previous studies have investigated neonatal conditions...

Innovation and Creation

Innovation and Creation

Effect of pyrrolidinedithiocarbamate on neural developmental disorder of adult offspring with maternal systemic exposure to Poly(I:C) during pregnancy

To explore the correlation between the elevated expression of cytokines under the induction of Poly(I:C) (polycytidylic acid) in maternal hosts and the abnormal behaviors of adult offsprings and understand the intervening effects of nuclear factor NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC). Poly(I:C) or saline was administered to model the maternal infection during early pregnancy in rats. And the expression of cytokines was blocked with PDTC. The maternal levels of tumor necrosis factor alpha and interleukin-10 were determined by ELISA (enzyme-linked immunosorbent assay). The adult offsprings on different treatments were then compared with regards to prepulse inhibition (PPI), passive avoidance and active avoidance. After the administration of Poly(I:C), there was an elevated levels of serum cytokines as shown by the markedly increased serum levels of IL-10 and TNF-α. The serum levels of IL-10 and TNF-α in the model group were significantly higher than those in the control group [(18.26 ± 1.52) pg/ml, (119.64 ± 16.42) pg/ml vs. (0.16 ± 0.13) pg/ml and (11.21 ± 1.81) pg/ml]. The elevation was partly blocked by PDTC. The serum levels of IL-10 and TNF-α in the intervention group [(12.64 ± 2.04) pg/ml and (30.34 ± 2.19) pg/ml respectively] were lower than those in the model group, but still higher than those in the control group. The psychotic-like phenotypes including defects in PPI, passive avoidance and active avoidance were observed in Poly(I:C)-treated offsprings. Such an effect was blunted by the PDTC intervention. The PPI results demonstrated that the PP₂ and PP₈ difference between rats in 3 groups were statistically significant, with a lower PPI value in the model group than in the intervention group, in the intervention group than in the control group and much lower in the model group than in the control group. PP4 was lower in the model group than that in the intervention group, and also lower in the model group than in the control group. There was no significant difference between the control group and the intervention group. The passive avoidance results indicated that T1 was higher in the model group than in the control and intervention groups and there was no statistical difference between the control and intervention groups. T2 was lower in the model group than in the control and intervention groups and there was no statistical difference between the control and intervention groups. And the active avoidance test results showed that total conditioned reflex times of the control group was higher than those of the intervention and model groups. No statistical difference was found between the intervention and model groups. Total reflex rate of the control group was higher than that of the intervention and model groups. No statistical difference was found between the intervention and model groups. PDTC can interfere with neural developmental disorder of adult offsprings through blunting the cytokine-mediated maternal immune response.

Does the “Dynamic Core” Approach Help to Manage Autistic Behavioral Disorders?

To the Editor: Autism is a neural development disorder in which some aspects of cognition, perception, and information-processing are disturbed. It seems that autistic patients have difficulties with processing complex situations. For example: 1) one main problem of autistic patients is their problematic involvement in social interactions, which are simply the hardest thing our brains have to process; 1 2) motion sensitivity of autistic patients is significantly decreased for second-order (texture-defined) stimuli; 2 3) auditory tests show that spectrally- and temporally dynamic tasks involving complex operations (evaluation, attention) are not performed appropriately in autistic persons. 3 We suggest that the abovementioned autistic behaviors may be interpreted by the dynamic core hypothesis (DCH) of consciousness. According to the DCH, consciousness arises from a group of neurons (the dynamic core), whose dynamics are simultaneously differentiated and integrated. Based on this view, in conscious states, the dynamic core integrates different pieces of input information that have high entropy and variability, leading to conscious perception of these complex inputs. 4 We suppose that ineffective dealing with complex stimuli in autistic patients may be the result of complexity-reduction in the dynamic core, which, in turn, leads to narrowing of consciousness. The cause of dynamic core complexity-reduction in autism may be related to some neurological findings: 1) some researchers suggest that atypical neural connectivity may lead to disturbed visual information-processing in autism; 2 and 2) The gray matter in the brain of autistic patients is locally decreased in the mirror-neuron system (MNS) areas. MNS is supposed to be the basis of empathic behavior, which has a key role in social interactions. Moreover, cortical thinning of MNS in areas involved in emotion and social behavior was correlated with autism severity. 5 We believe that behavioral treatment may help to repair the dynamic core defect in autistic patients. We propose that interacting with complex inputs at different levels of complexity must be taught to autistic patients. In accordance with our idea, some researchers have found that proper reward can increase response variability in autistic patients. 6 This

151 Neonatal Complications and Autism Spectrum Disorders

Background and aims: Autism spectrum disorders (ASDs) are disorders of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Previous studies investigating neonatal factors and ASDs have produced inconsistent results. We performed confirmatory analyses concerning various neonatal complications and a later diagnosis with ASDs, and infantile autism, specifically.Methods: A Danish population based cohort study, including all children born in Denmark from 1994, through 2002, a total of 604,140 children. Diagnoses of neonatal complications were retrieved from the Danish National Hospital Register. Children diagnosed with ASDs were identified using the Danish Psychiatric Central Register. Data was analyzed using Cox proportional hazards regression.Results: A total of 4,145 children were diagnosed with ASDs, of which 1,493 had infantile autism. We found an increased risk of ASDs after exposure to a variety of neonatal complications; respiratory distress: adjusted hazard ratio (HR)=1.24 [95% confidence interval (CI): 1.02-1.51], intracranial bleeding, cerebral edema or seizures: HR=1.94 [95% CI: 1.12-3.36], neonatal hypoglycemia: HR=1.46 [95% CI: 1.11-1.93], and neonatal septicemia: HR=1.59 [95% CI: 1.21-2.10]. Generally, the increased risk of ASDs after neonatal complication was most prominent for children born preterm. Same pattern of association was found for infantile autism.Conclusions: Different neonatal complications are likely to cause neurological damage and alter brain development, and hence increase the risk of ASDs, and infantile autism. This effect seems to be mediated through different pathways including lack of oxygen, glucose, and possibly through activated immune function during early neonatal life.

Participation in leisure activities among boys with attention deficit hyperactivity disorder

ADHD is a neural developmental disorder expressed in various life settings. Yet, previous studies have focused mainly on children's function in school and academic achievement. The purpose of the present study was, therefore, to examine participation patterns in outside formal school activities among boys with ADHD compared to typical boys. Participants included 25 boys aged 8–11 years with ADHD and 25 age-matched typical boys. All participants completed the Children's Assessment of Participation and Enjoyment (CAPE). Several aspects of participation were examined: diversity, intensity, enjoyment, place, and partners in 49 extra curricular activities. The findings indicate that boys with ADHD reported significant lower intensity rates of participation in most activity domains. Furthermore, boys with ADHD also reported higher diversity scores and lower enjoyment in ‘formal’ activities. Yet, no significant differences were found with regard to activity place and partners. These findings enhance the importance of providing therapy that refers to after school activities. Accordingly, CAPE can be useful for assessing boys with ADHD and planning appropriate intervention programs.

Cell type-dependent, infection-induced, aberrant DNA methylation in gastric cancer

Epigenetic changes correspond to heritable modifications of the chromatin structure, which do not involve any alteration of the DNA sequence but nonetheless affect gene expression. These mechanisms play an important role in cell differentiation, but aberrant occurrences are also associated with a number of diseases, including cancer and neural development disorders. In particular, aberrant DNA methylation induced by H. Pylori has been found to be a significant risk factor in gastric cancer. To investigate the sensitivity of different genes and cell types to this infection, a computational model of methylation in gastric crypts is developed. In this article, we review existing results from physical experiments and outline their limitations, before presenting the computational model and investigating the influence of its parameters.

Investigating the characteristics of educational computer games developed for children with autism: a project proposal

Autism is a neural developmental disorder that interfere the brain development and causes deficit in social interaction and communication skills as a result. One of the most important outcomes of education of children with autism is the functional independence skills. Effective instructional techniques and methods are immensely important for children with autism to improve their functional independence skills. At this point we think that since playing is a fundamental part of a child's physical, cognitive, linguistic, emotional and social development, educational computer games which are used effectively in education of children without developmental disorders can also be used effectively in education of children with autism. This paper proposes a project for investigating how children with autism interact with computer games, how computer games can be used for educational purposes, and what characteristics educational computer games should have in education of children with autism. For this project educational computer games for children with autism will be designed and developed. In this process, design based research methodology will be used to investigate the characteristics of educational computer games for children with autism.

Axon Growth and Guidance: Receptor Regulation and Signal Transduction

The development of precise connectivity patterns during the establishment of the nervous system depends on the regulated action of diverse, conserved families of guidance cues and their neuronal receptors. Determining how these signaling pathways function to regulate axon growth and guidance is fundamentally important to understanding wiring specificity in the nervous system and will undoubtedly shed light on many neural developmental disorders. Considerable progress has been made in defining the mechanisms that regulate the correct spatial and temporal distribution of guidance receptors and how these receptors in turn signal to the growth cone cytoskeleton to control steering decisions. This review focuses on recent advances in our understanding of the mechanisms mediating growth cone guidance with a particular emphasis on the control of guidance receptor regulation and signaling.

Characteristics of a spina bifida population including North American Caucasian and Hispanic individuals.

Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes. A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and association testing using the transmission disequilibrium test. A total of 509 affected child/parent trios and 309 affected child/parent duos have been enrolled to date for genetic association studies. Subsets of the patients have also been enrolled for studies assessing development, brain imaging, and neurocognitive outcomes. The study recruited two major ethnic groups, with 45.9% Hispanics of Mexican descent and 36.2% North American Caucasians of European descent. The remaining patients are African-American, South and Central American, Native American, and Asian. Studies of this group of patients have already discovered distinct corpus callosum morphology and neurocognitive deficits that associate with MM. We have identified maternal MTHFR 667T allele as a risk factor for MM. In addition, we also found that several genes for glucose transport and metabolism are potential risk factors for MM. The enrolled patient population provides a valuable resource for elucidating the disease characteristics and mechanisms for MM development.

Assessing Neural Stem Cell Motility Using an Agarose Gel-based Microfluidic Device

While microfluidic technology is reaching a new level of maturity for macromolecular assays, cell-based assays are still at an infant stage. This is largely due to the difficulty with which one can create a cell-compatible and steady microenvironment using conventional microfabrication techniques and materials. We address this problem via the introduction of a novel microfabrication material, agarose gel, as the base material for the microfluidic device. Agarose gel is highly malleable, and permeable to gas and nutrients necessary for cell survival, and thus an ideal material for cell-based assays. We have shown previously that agarose gel based devices have been successful in studying bacterial and neutrophil cell migration. In this report, three parallel microfluidic channels are patterned in an agarose gel membrane of about 1mm thickness. Constant flows with media/buffer are maintained in the two side channels using a peristaltic pump. Cells are maintained in the center channel for observation. Since the nutrients and chemicals in the side channels are constantly diffusing from the side to center channel, the chemical environment of the center channel is easily controlled via the flow along the side channels. Using this device, we demonstrate that the movement of neural stem cells can be monitored optically with ease under various chemical conditions, and the experimental results show that the over expression of epidermal growth factor receptors (EGFR) enhances the motility of neural stem cells. Motility of neural stem cells is an important biomarker for assessing cells aggressiveness, thus tumorigenic factor. Deciphering the mechanism underlying NSC motility will yield insight into both disorders of neural development and into brain cancer stem cell invasion.

Neural progenitor cells and developmental disorders

Neural stem/multipotent progenitor cells are present within periventricular generative zones along the entire neuraxis throughout neural development and during adult life. These cells give rise to all of the major cellular elements of the brain, including neurons, oligodendroglia, and astrocytes. Recent studies suggest that cells with a similarly broad lineage potential are also present in postmigratory domains of the postnatal and the adult cerebral cortex. Neural stem cells are defined by a number of properties, including their ability to undergo constitutive proliferation, to maintain themselves (self-renew), to generate large numbers of progeny through transient amplification of intermediate progenitor pools, and to generate new cells in response to injury or disease. These primordial neural cells undergo progressive lineage restriction and commitment to specific neuronal and glial phenotypes in response to cascades of cytokines and the induction of positive and negative transcriptional regulators. These cytokines regulate a range of interrelated cellular processes, including activation, proliferation, viability, lineage commitment, and progressive stages of neuronal and glial lineage maturation. The detailed definition of developmental pathways responsible for neurogenesis and gliogenesis in the mammalian brain will further our understanding of the molecular and cellular basis of mental retardation and other pervasive neurologic disorders of childhood. Further, these cumulative studies suggest that a broad array of neural regenerative strategies, including gene and progenitor cell replacement and activation of endogenous cellular populations, may allow structural and functional reconstitution of neural circuits damaged as a consequence of a spectrum of neurodevelopmental disorders. MRDD Research Reviews 1998; 4:143–149. © 1998 Wiley-Liss, Inc.