Epigenetics comes to Life: Neurodevelopmental disorders (NDDs) encompass a broad group of conditions characterized by alterations in the development of the central nervous system (CNS), resulting in varying degrees of cognitive and/or behavioral symptoms. Several conditions are grouped under the diagnosis of NDD, including intellectual disability (ID), learning disorders, communication disorders, motor disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum condition (ASC), epileptic encephalopathies (EE), and schizophrenia (SZ) [1, 2]. In the “Journal Nature Neuroscience”: Intelligence ‘Networks’ Discovered In Brain For The First Time, 2015-“Remarkably, they found that some of the same genes [M1 & M3] HERE that influence human intelligence in healthy people were also the same genes that cause impaired cognitive ability and epilepsy when mutated.” “Also, studies show that autistic people have a 20% risk of having epilepsy and that people with epilepsy have a 20% chance of being autistic. The reason for this may be that the effects of epilepsy and autism spectrum condition (ASC) on brain structure and function overlap. Chromosome 12-GRIN2B The NMDA receptors mediate a slow -permeable component of excitatory synaptic transmission in the central nervous system. The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum condition, attention deficit hyperactivity disorder, epilepsy, and schizophrenia.
Autism spectrum condition (ASC) and dyslexia are both neurodevelopmental disorders with high prevalence in children. These two disorders share common genetic risks remain elusive. DOCK4 (dedicator for cytokinesis 4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1, is one of few genes that are associated with both autism spectrum condition (ASC) and dyslexia. Dock4 is important for neuronal development and social behaviors. Likewise, recent research examining polygenetic risk has revealed several significant associations between dyslexia risk and genetic liability to several neuropsychiatric and neurodevelopmental disorders and problems (Gialluisi et al., 2020). Thus, polygenic inheritance is the phenotypic trait that is not a single gene trait but a cumulative expression of multiple genes. What are other polygenic inheritance examples? Human phenotypes or human physical traits such as hair color, height, skin color, blood pressure, intelligence, autism, and longevity. [Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488083/; https://www.frontiersin.org/articles/10.3389/fncel.2019.00577/full; https://onlinelibrary.wiley.com/doi/10.1002/dys.1681?fbclid=IwAR3pdYZTYwoFMSFASW8CDJwzOpyNRVpMyt38K0_K-4IweECeBJZIrNbmaSE;https://www.biologyonline.com/dictionary/polygenic-inheritance].
Note: New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has found that some processes behind the early development of GABAergic neurons, neurons that produce the main inhibitory chemical messenger in the central nervous system, are consistent between humans and mice. Many of these disorders have overlapping genetics and phenotypes and changes in striatal and cortical GABAergic neurons have been robustly documented in both autism and schizophrenia.” [Retrieved from https://neurosciencenews.com/gaba-neurodevelopment-asd-19784/].
What is the Interoceptive System? Having trouble with this sense can also make self-regulation a challenge because of physiological processes related to affective feeling. The interoceptive system [also] has special nerve receptors which are located throughout our bodies including internal organs, bones, muscles, and skin. These receptors send information to the brain. The brain interprets this information and uses it to tell us how we feel. The interoceptive system helps our bodies stay in a state of optimal balance, which is known as homeostasis. [Retrieved from https://occupationaltherapy.com.au/interoception]. Especially, it’s hard for those with Interoceptive Discrimination Disorder (IDD), which is a form of Sensory Processing Disorder (SPD), it is very difficult to distinguish internal feelings from external ones. [Retrieved from http://sinetwork.org/the-other-senses-interoception/].
Note: A study found impaired functional connectivity and autistic-like behaviors in CX3CR1−/− mice lacking responsive microglia (Zhan and others 2014), for example, though this could be due to two reasons: a transient decreased microglial density in postnatal development, or the fractalkine signaling pathway being responsible for the tagging of synapses. Also, a new study expressed by microglia—the immune cells of the central nervous system—TAMs perform bona fide immune-related roles as regulation of inflammation and cytokine secretion both in health and in disease such as Alzheimer’s and Parkinson’s disease, ischemia, and multiple sclerosis. Likewise, TAM receptor MERTK expression is enriched in the central nervous system and in resident innate immune cells where it regulates numerous functions that support brain plasticity. [Retrieved from https://neurosciencenews-com.cdn.ampproject.org/c/s/neurosciencenews.com/neuroimmune-brain-plasticity-19663/amp/?fbclid=IwAR2-b73FidTuEOXEratUhsXrvKD9Be9PWOVfCRsYTAG8IDColpka5Lm3EpM].
Alzheimer’s disease is the most prevalent neurodegenerative disease in aging, affecting approximately 46 million people worldwide. Theories point to a number of potential causes, including age-related changes in the brain, along with genetic, environmental, and lifestyle factors. These lead to the accumulation of toxic proteins in the brain—and according to recent evidence, immune system changes—that result in loss of neurons and their connections. To examine how the brain’s immune cells may contribute to Alzheimer’s disease, Dr. Gan and her colleagues first established the molecule fingerprint of individual microglia in the brains of patients with Alzheimer’s disease who carry a mutation in the TREM2 gene that markedly elevates the individual’s risk for developing Alzheimer’s disease.
TREM2 is a receptor mainly expressed by microglia in the brain, and among other functions, it signals through an enzyme named AKT to modulate inflammation and metabolism. [Retrieved from https://neurosciencenews-com.cdn.ampproject.org/c/s/neurosciencenews.com/microglia-alzheimers-prevention-19732/amp/?fbclid=IwAR3S_hUbO5cJNy6VkvsGhp7GZ3Q5bPaeFeksIC_XiAjce4_wgAxSF7arEiM; https://www.science.org/doi/10.1126/scitranslmed.abe3947].