Biological Understanding of Neurodevelopmental Disorders Based on Epigenetics, a New Genetic Concept in Education

Neurodevelopmental disorders, such as autism spectrum disorder, attention deficit hyperactive disorder, and learning disabilities, are heterogeneous conditions that are thought to have a multifactorial etiology including congenital genetic abnormalities and acquired environmental factors. Epigenetics is a biological mechanism that controls gene expression based on chemical modifications of DNA and chromosomal histone proteins. Environmental factors, such as severe mental stress, have been demonstrated to alter gene expression by changing epigenetic chemical modifications in the brain. Therefore, epigenetics is not only involved in congenital autism spectrum disorder-like conditions (e.g., Prader-Willi syndrome and Rett syndrome) but may also be involved in acquired attention deficit hyperactive disorder-like conditions (e.g., via child abuse and neglect). In this chapter, we introduce the basis of the epigenetic mechanism and the recent biological understanding of neurodevelopmental disorders based on epigenetics, which is a new genetic concept not only in medicine but also in education, which bridges internal brain mechanisms and external environmental factors.

Cav1.2 Activity and Downstream Signaling Pathways in the Hippocampus of An Animal Model of Depression

Functional and morphological modifications in the brain caused by major mood disorders involve many brain areas, including the hippocampus, leading to cognitive and mood alterations. Cav1.2 channel expression has been found to increase in animals with depressive-like behaviors. Calcium influx through these channels is associated with changes in excitation-transcriptional coupling by several intracellular signal pathways that are regulated by its C-terminus region. However, which of these signaling pathways is activated during the development of depressive-like behaviors is not known. Here, we evaluate the phosphorylation and expression levels of crucial kinases and transcription factors at the hippocampus of rats after 21 days of chronic restraint stress. Our results show that rats subjected to CRS protocol achieve less body weight, have heavier adrenal glands, and exhibit depression-like behaviors such as anhedonia, behavioral despair and decreased social interaction. Cav1.2 mRNA and protein expression levels, plus l-type calcium current amplitude, are also increased in treated rats when compared with control animals. Out of the three main signaling pathways activated by l-type currents, we only observed an increment of CaM-NFAT axis activity with the concomitant increment in Fas ligand expression. Thus, our results suggest that CRS activates specific pathways, and the increased expression of Cav1.2 could lead to neuronal death in the hippocampus.

Cortical GABAergic Interneurons in Cross-Modal Plasticity following Early Blindness

Early loss of a given sensory input in mammals causes anatomical and functional modifications in the brain via a process called cross-modal plasticity. In the past four decades, several animal models have illuminated our understanding of the biological substrates involved in cross-modal plasticity. Progressively, studies are now starting to emphasise on cell-specific mechanisms that may be responsible for this intermodal sensory plasticity. Inhibitory interneurons expressing γ-aminobutyric acid (GABA) play an important role in maintaining the appropriate dynamic range of cortical excitation, in critical periods of developmental plasticity, in receptive field refinement, and in treatment of sensory information reaching the cerebral cortex. The diverse interneuron population is very sensitive to sensory experience during development. GABAergic neurons are therefore well suited to act as a gate for mediating cross-modal plasticity. This paper attempts to highlight the links between early sensory deprivation, cortical GABAergic interneuron alterations, and cross-modal plasticity, discuss its implications, and further provide insights for future research in the field.