scholarly journals Dynamic N6-methyladenosine RNA methylation in brain and diseases

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Andrew M Shafik ◽  
Emily G Allen ◽  
Peng Jin

N6-methyladenosine (m6A) is a dynamic RNA modification that regulates various aspects of RNA metabolism and has been implicated in many biological processes and transitions. m6A is highly abundant in the brain; however, only recently has the role of m6A in brain development been a focus. The machinery that controls m6A is critically important for proper neurodevelopment, and the precise mechanisms by which m6A regulates these processes are starting to emerge. However, the role of m6A in neurodegenerative and neuropsychiatric diseases still requires much elucidation. This review discusses and summarizes the current body of knowledge surrounding the function of the m6A modification in regulating normal brain development, neurodegenerative diseases and outlines possible future directions.

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Stephen W. Briggs ◽  
Aristea S. Galanopoulou

The incidence of seizures is particularly high in the early ages of life. The immaturity of inhibitory systems, such as GABA, during normal brain development and its further dysregulation under pathological conditions that predispose to seizures have been speculated to play a major role in facilitating seizures. Seizures can further impair or disrupt GABAAsignaling by reshuffling the subunit composition of its receptors or causing aberrant reappearance of depolarizing or hyperpolarizing GABAAreceptor currents. Such effects may not result in epileptogenesis as frequently as they do in adults. Given the central role of GABAAsignaling in brain function and development, perturbation of its physiological role may interfere with neuronal morphology, differentiation, and connectivity, manifesting as cognitive or neurodevelopmental deficits. The current GABAergic antiepileptic drugs, while often effective for adults, are not always capable of stopping seizures and preventing their sequelae in neonates. Recent studies have explored the therapeutic potential of chloride cotransporter inhibitors, such as bumetanide, as adjunctive therapies of neonatal seizures. However, more needs to be known so as to develop therapies capable of stopping seizures while preserving the age- and sex-appropriate development of the brain.


2007 ◽  
Vol 13 (6) ◽  
pp. 1072-1073
Author(s):  
Doug Johnson-Greene

Brain Development: Normal Processes and the Effects of Alcohol and Nicotine. Michael W. Miller (Ed.). 2006. New York: Oxford University Press, 424 pp., $98.50 (HB)The process of brain development is an essential yet often overlooked area in the neuropsychological literature. The topic has a natural appeal to those who work with children where developmental disorders predominate. However, it is often more difficult for those who work with adults to appreciate the role of developmental aberrations and their contribution to pathological processes that may seem far removed from the early developmental history of our patients. The tendency for some to deemphasize early developmental influences may stem in part from a lack of clarity about how common toxin exposures, such as alcohol and nicotine, alter normal brain development and contribute to changes in cognitive function. Increasingly, evidence of early developmental influences has emerged in a host of epigenetically-based developmental disorders and neuropathological conditions, such as schizophrenia, and these influences are also implicated in theoretical models, such as cognitive reserve.


2021 ◽  
Vol 14 (02) ◽  
pp. 663-669
Author(s):  
Kirthika C P ◽  
Siva T ◽  
Rajeswaran R ◽  
Kalpana R ◽  
Yuvaraj Maria Francis

Introduction: Corpus callosum (CC) is the largest commissural white fibres interconnecting cerebral hemispheres. The corpus callosum is responsible for interhemispheric transfer of information which is essential for cognitive function. The foetal corpus callosum serves as sensitive indicator for normal brain development and maturation. As the corpus callosum is a part of the highest order latest maturing mental network of the brain, its measurements are important to assess normal brain development and to locate structural changes. A comprehensive evaluation of normal human foetal corpus callosal development is essential to detect and understand the congenital anomalies of the brain. Thus, the prenatal diagnosis of partial or complete agenesis of the corpus callosum is important for predicting the normal development of the foetus. Foetal neural anomalies that are suspected on prenatal ultrasonography (USG) can be detected in early stage using foetal MRI. This imaging technique is highly useful for detailed visualization of normal neural development. Certain conditions like colpocephaly and widening of interhemispheric fissure can be clearly visualized using foetal MRI when compared to prenatal ultrasonography. Aim and objective: Was to establish the normal reference values for the measurement of foetal corpus callosum. The length and thickness of the foetal CC was measured corresponding to gestational age (GA) between 18-36weeks. Materials and methods: A retrospective MRI study was carried out in Radiology department of Sri Ramachandra Hospital. The study was conducted on 50 pregnant women with GA of 18-32 weeks and morphology of foetal corpus callosum was measured using MRI. The corpus callosum was visualized in a mid-sagittal plane as an anechoic structure, delimited by two echogenic lines superiorly by sulcus of the corpus callosum and inferiorly by the septum pellucidum. The length of corpus callosum was measured from the anterior most aspect of genu to the posterior most aspect of the splenium and the width of individual parts were measured and correlated with gestational age. The values obtained from the study were statistically calculated using regression coefficient method. Results: In the present study following parameters were observed such as length and width of diverse parts of Corpus callosum. The length of foetal CC ranged from 25.96 to 47.2 mm in 18 to 32 weeks of gestational age. The range of width of rostrum, genu, body and splenium were 1.2 to 2.2 mm, 1.2-2.8mm, 1.3-3.1mm and 1.36-3.2mm respectively. Conclusion: The periodic development of nervous system can be calculated more effectively with the morphometric measurement of foetal CC and its correlation with BPD. It is considered to be accurate than using BPD measurement of head circumference in USG. Hence, with the normative data of foetal CC measurements correlated with gestational age would give us accurate details of neuronal growth rather than measuring biparietal diameter (BPD) alone using USG. This knowledge will be highly helpful for the gynaecologists to predict the abnormal development of the foetus and it is advised to include foetal CC parameters as a one of the tools for early detection of CNS anomalies.


Author(s):  
James C. Harris

Intellectual disability is a neurodevelopmental disorder that continues throughout the life span of the affected person. It is essential to understand how persons with intellectual disability progress throughout their life span from infancy to old age. The maturation of the brain, their environmental experiences, and the mastery of developmental challenges and tasks must all be considered. A focus on brain development is in keeping with neuroscience research indicating that progressive brain maturation is accompanied by successive synaptic reorganization as one moves from one developmental stage to the next. Anatomical Magnetic Resonance Imaging Studies are playing a major role in understanding the developmental trajectories of normal brain development (Durston et al., 2001; Giedd et al., 1999). Understanding the developmental trajectories of normal brain development is crucial to the interpretation of brain development in neurodevelopmental disabilities. During normal development, white matter volume increases with age, and although gray matter volumes increase during childhood, they decrease before adulthood. These changes in the brain are accompanied by changes in cognitive processing; for example, executive functioning shows a progressive emergence from the preschool years (Espy et al., 1999) into the adolescent years. Working memory and inhibitory processes may be measured during the preschool years. By adolescence, abstract reasoning, anticipatory planning, and mental judgment have emerged and may be measured. Cognitive abilities in adolescence are qualitatively different from those of young children as a result of the reorganization of the prefrontal cortex during maturation. How genetic background and environment interact in producing these changes is the object of ongoing study, yet investigators are beginning to understand how physiological processes of synaptic development, circuits, and neuronal network formation relate to processes of cognitive development (Fossella et al., 2003). The development of persons with intellectual disability is now being evaluated systematically, and developmental trajectories are being established for known neurogenetic syndromes. These studies are making up for a surprising lack of application of a developmental perspective to persons with intellectual disability. Developmental theorists have, for the most part, monitored and measured development in normally intelligent persons in establishing developmental landmarks.


Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3453-3465 ◽  
Author(s):  
A. Stoykova ◽  
R. Fritsch ◽  
C. Walther ◽  
P. Gruss

Pax6 is a member of the Pax gene family of transcriptional regulators that exhibits a restricted spatiotemporal expression in the developing central nervous system, eye and nose. Mutations in Pax6 are responsible for inherited malformations in man, rat and mouse. To evaluate the role of Pax6 in forebrain development, we studied in detail mouse Small eye/Pax6 mutant brains. This analysis revealed severe defects in forebrain regions where Pax6 is specifically expressed. The establishment of some expression boundaries along the dorsoventral axis of the secondary prosencephalon is distorted and the specification of several ventral structures and nuclei is abolished. Specifically, the development of the hypothalamo-telencephalic transition zone and the ventral thalamus is distorted. Our detailed analysis included a comparison of the expression of Pax6, Dlx1 and several other genes during embryonic mouse brain development in wild-type and in the mutant Small eye (Sey) brain. The results from the analysis of normal brain development show that the restricted expression of Pax6 and Dlx1 at E12.5 dpc respect domains within the forebrain, consistent with the implications of the prosomeric model for the organisation of the forebrain (L. Puelles and J. L. R. Rubenstein (1993) Trends Neurosci. 16, 472–479). Furthermore, we found an early restriction of Pax6 and Dlx1 expression into presumptive histogenetic fields that correlate with the formation of distinct forebrain structures and nuclei. Our results are discussed in light of changes in adhesive properties in the Sey brain that might control segregation, assembly and cell migration of progenitors of specific forebrain regions.


Author(s):  
Igor Ponomarev

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.


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