Cellular and molecular mechanisms of neurodevelopmental disorders

Ghiani, Cristina A.; Faúndez, Víctor

doi:10.1002/jnr.24041

Cited by 10 publications

(6 citation statements)

References 33 publications

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“…Genetic polymorphisms that generate loss of BLOC-1 function have been proposed to increase the risk of developing IDD (reviewed by Hartwig et al, 2018 ) perhaps in concert with other partner genes. These findings are in line with the hypothesis that neurodevelopmental disorders result from the interplay of more than one malfunctioning gene, explaining the overlapping phenotypes for some of these syndromes ( Ghiani and Faundez, 2017 and references herein; Gandal et al, 2018 ). Recently, a 6-yr-old boy, who carries a mutation in dysbindin, was reported to display speech and other developmental delays ( Bryan et al, 2017 ).…”

Section: Discussionsupporting

confidence: 88%

Sleep/Wake Disruption in a Mouse Model of BLOC-1 Deficiency

et al. 2018

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Mice lacking a functional Biogenesis of Lysosome-related Organelles Complex 1 (BLOC-1), such as those of the pallid line, display cognitive and behavioural impairments reminiscent of those presented by individuals with intellectual and developmental disabilities. Although disturbances in the sleep/wake cycle are commonly lamented by these individuals, the underlying mechanisms, including the possible role of the circadian timing system, are still unknown. In this paper, we have explored sleep/circadian malfunctions and underlying mechanisms in BLOC-1-deficient pallid mice. These mutants exhibited less sleep behaviour in the beginning of the resting phase than wild-type mice with a more broken sleeping pattern in normal light-dark conditions. Furthermore, the strength of the activity rhythms in the mutants were reduced with significantly more fragmentation and lower precision than in age-matched controls. These symptoms were accompanied by an abnormal preference for the open arm in the elevated plus maze in the day and poor performance in the novel object recognition at night. At the level of the central circadian clock (the suprachiasmatic nucleus, SCN), loss of BLOC-1 caused subtle morphological changes including a larger SCN and increased expression of the relative levels of the clock gene Per2 product during the day but did not affect the neuronal activity rhythms. In the hippocampus, the pallid mice presented with anomalies in the cytoarchitecture of the Dentate Gyrus granule cells, but not in CA1 pyramidal neurones, along with altered PER2 protein levels as well as reduced pCREB/tCREB ratio during the day. Our findings suggest that lack of BLOC-1 in mice disrupts the sleep/wake cycle and performance in behavioural tests associated with specific alterations in cytoarchitecture and protein expression.

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Section: Discussionsupporting

confidence: 88%

Sleep/Wake Disruption in a Mouse Model of BLOC-1 Deficiency

et al. 2018

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“…Negative environmental factors include maternal nutritional, medical and distress factors, and hypoxia/ischemia. Emerging evidence shows that such prenatally and early postnatally acquired “neuroanatomy” changes (Donovan & Basson, 2017) partially underlie behavioral and cognitive changes, including those observed in common neurodevelopmental and psychiatric disorders (Deoni et al, 2014; Ghiani & Faundez, 2017; Haroutunian et al, 2014; Ziats et al, 2015). Positive environmental factors, such as getting breastfed for a period of at least 3 months, is shown to have a developmental advantage (i.e., a positive effect on WM microstructure in late maturing frontal and association brain regions; Deoni et al, 2013).…”

Section: Development Of the Human Brain: Insights From Physical Modelmentioning

confidence: 99%

“…Neurodevelopmental disorders have a strong genetic bias, but in recent years causal environmental factors have been identified. Genetic, epigenetic, and prenatal environmental exposure factors may interact during brain development vulnerability windows and lead to disorders in ways that are not yet clearly understood (Davis et al, 2016; Ghiani & Faundez, 2017; Van den Bergh et al, 2017). While basic and translation research that focused on task-related brain activation has increased our understanding of underlying neural substrates of particular cognitive, emotional, and social behavior and how their alternations underlie psychopathology, the focus has been shifted to the study of neural circuits rather than on specific brain regions (Barch & Carter, 2016).…”

Section: Putative Prenatal Origins Of Developmental and Psychiatric Dmentioning

confidence: 99%

Prenatal stress and the developing brain: Risks for neurodevelopmental disorders

Bergh

Dahnke

Mennes³

2018

Dev Psychopathol

120

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The prenatal period is increasingly considered as a crucial target for the primary prevention of neurodevelopmental and psychiatric disorders. Understanding their pathophysiological mechanisms remains a great challenge. Our review reveals new insights from prenatal brain development research, involving (epi)genetic research, neuroscience, recent imaging techniques, physical modeling, and computational simulation studies. Studies examining the effect of prenatal exposure to maternal distress on offspring brain development, using brain imaging techniques, reveal effects at birth and up into adulthood. Structural and functional changes are observed in several brain regions including the prefrontal, parietal, and temporal lobes, as well as the cerebellum, hippocampus, and amygdala. Furthermore, alterations are seen in functional connectivity of amygdalar-thalamus networks and in intrinsic brain networks, including default mode and attentional networks. The observed changes underlie offspring behavioral, cognitive, emotional development, and susceptibility to neurodevelopmental and psychiatric disorders. It is concluded that used brain measures have not yet been validated with regard to sensitivity, specificity, accuracy, or robustness in predicting neurodevelopmental and psychiatric disorders. Therefore, more prospective long-term longitudinal follow-up studies starting early in pregnancy should be carried out, in order to examine brain developmental measures as mediators in mediating the link between prenatal stress and offspring behavioral, cognitive, and emotional problems and susceptibility for disorders.

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“…Early life stress has been recognized as a key mediator of developmental programming, since a limited insult during developmental vulnerability windows may increase the risk for either subclinical neuropsychological alterations or clinical conditions, such as neurodevelopmental disorders ( Reynolds et al, 2013 ; Ghiani and Faundez, 2017 ; Pervanidou et al, 2017 ). It has been suggested that ELS, precisely prenatal maternal stress (PMS) and infant stress, is a risk factor for ASD ( Beversdorf et al, 2018 ; Magariños et al, 2018 ).…”

Section: Stress System Developmental Trajectory and The Role Of Early Life Stressmentioning

confidence: 99%

Stress System Activation in Children and Adolescents With Autism Spectrum Disorder

et al. 2022

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The mission of the human stress system is the maintenance of homeostasis in the presence of real or perceived, acute or chronic stressors. The hypothalamic–pituitary–adrenal (HPA) axis and the autonomic nervous system (ANS) are the stress system-related neuroendocrine pathways. There is abundant evidence that children and adolescents with autism spectrum disorder (ASD) may exhibit atypical function within the HPA axis and the ANS both at the resting state and during the presence of social and/or non-social stressors. The aim of this review is to provide an up-to-date summary of the findings regarding stress system alterations in children and adolescents with ASD. We focus on the variations of stress hormones circadian rhythms, specifically cortisol and alpha-amylase (i.e., a surrogate index of epinephrine/norepinephrine secretion), and on the alterations of stress system responsivity to different stressors. Also, we present imaging and immunological findings that have been associated with stress system dysregulation in children and adolescents with ASD. Finally, we review the pivotal role of HPA axis-ANS coordination, the developmental trajectory of the stress system in ASD, and the possible role of early life stress in the dysregulation of the stress system demonstrated in children and adolescents with ASD. This synthesis will hopefully provide researchers with a foundation for an integrated approach to future research into stress system variations in children and adolescents with ASD.

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Cellular and molecular mechanisms of neurodevelopmental disorders

Cited by 10 publications

References 33 publications

Sleep/Wake Disruption in a Mouse Model of BLOC-1 Deficiency

Sleep/Wake Disruption in a Mouse Model of BLOC-1 Deficiency

Prenatal stress and the developing brain: Risks for neurodevelopmental disorders

Stress System Activation in Children and Adolescents With Autism Spectrum Disorder

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