Human-genome single nucleotide polymorphisms affecting transcription factor binding and their role in pathogenesis.

Single nucleotide polymorphisms (SNPs) are the most common type of variation in the human genome. The vast majority of SNPs identified in the human genome do not have any effect on the phenotype; however, some can lead to changes in the function of a gene or the level of its expression. Most SNPs associated with certain traits or pathologies are mapped to regulatory regions of the genome and affect gene expression by changing transcription factor binding sites.

Once induced, it lasts for a long time: the structural and molecular signatures associated with depressive-like behavior after neonatal immune activation.

Adverse factors such as stress or inflammation in the neonatal period can affect the development of certain brain structures and have negative delayed effects throughout the lifespan of an individual, by reducing cognitive abilities and increasing the risk of psychopathologies. One possible reason for these delayed effects is the neuroinflammation caused by neonatal immune activation (NIA). Neuroinflammation can lead to disturbances of neurotransmission and to reprogramming of astroglial and microglial brain cells; when combined, the two problems can cause changes in the cytoarchitecture of individual regions of the brain.

Chromatin remodeling in oligodendrogenesis.

Oligodendrocytes are one type of glial cells responsible for myelination and providing trophic support for axons in the central nervous system of vertebrates. Thanks to myelin, the speed of electrical-signal conduction increases several hundred-fold because myelin serves as a kind of electrical insulator of nerve f ibers and allows for quick saltatory conduction of action potentials through Ranvier nodes, which are devoid of myelin. Given that different parts of the central nervous system are myelinated at different stages of development and most regions contain both myelinated and unmyelinated axons, it is obvious that very precise mechanisms must exist to control the myelination of individual axons.

Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases.

The vast majority of the genetic variants (mainly SNPs) associated with various human traits and diseases map to a noncoding part of the genome and are enriched in its regulatory compartment, suggesting that many causal variants may affect gene expression. The leading mechanism of action of these SNPs consists in the alterations in the transcription factor binding via creation or disruption of transcription factor binding sites (TFBSs) or some change in the affinity of these regulatory proteins to their cognate sites. In this review, we first focus on the history of the discovery of regulatory SNPs (rSNPs) and systematized description of the existing methodical approaches to their study.

The Effects of Chronic Stress on Brain Myelination in Humans and in Various Rodent Models.

The myelination of axons, which is performed in brain tissues by specialized glial cells (oligodendrocytes) is crucial for correct formation of the complicated neural circuitry necessary for normal cognition, sensation, and motor function. Myelin-related anomalies are seen in many neurodegenerative diseases and in psychiatric disorders, including major depressive disorder and post-traumatic stress disorder. Chronic stress involving chronic stress early in life is believed to be a major etiological factor of neuropsychiatric disorders.