Epigenetic Regulation as a Basis for Long-Term Changes in the Nervous System: In Search of Specificity Mechanisms

Abstract

Adaptive long-term changes in the functioning of nervous system (plasticity, memory) are not written in the genome, but are directly associated with the changes in expression of many genes comprising epigenetic regulation. Summarizing the known data regarding the role of epigenetics in regulation of plasticity and memory, we would like to highlight several key aspects. (i) Different chromatin remodeling complexes and DNA methyltransferases can be organized into high-order multiprotein repressor complexes that are cooperatively acting as the “molecular brake pads”, selectively restricting transcriptional activity of specific genes at rest. (ii) Relevant physiological stimuli induce a cascade of biochemical events in the activated neurons resulting in translocation of different signaling molecules (protein kinases, NO-containing complexes) to the nucleus. (iii) Stimulus-specific nitrosylation and phosphorylation of different epigenetic factors is linked to a decrease in their enzymatic activity or changes in intracellular localization that results in temporary destabilization of the repressor complexes. (iv) Removing “molecular brakes” opens a “critical time window” for global and local epigenetic changes, triggering specific transcriptional programs and modulation of synaptic connections efficiency. It can be assumed that the reversible post-translational histone modifications serve as the basis of plastic changes in the neural network. On the other hand, DNA methylation and methylation-dependent 3D chromatin organization can serve a stable molecular basis for long-term maintenance of plastic changes and memory.

Hypnotherapy and IBS: Implicit, long-term stress memory in the ENS?

“…Furthermore, several studies have suggested that long-term memory (LTM) may exist by epigenetic mechanisms at the cellular level [ [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] These findings support the notion that simple stress-induced implicit LTM may also persist throughout life by epigenetic mechanisms in the ENS.…”

An Overview of the Epigenetic Modifications in the Brain under Normal and Pathological Conditions

“…Oxidative stress [169], chronic inflammation [170], changes in chromatin remodeling [171], dysregulation of the enzymes involved in histone regulation [172], senescent cells [173], and telomere shortening [174] are among the several factors that may contribute to histone epigenetic changes in the aging brain.…”

Malaria in the ‘Omics Era’

“…However, in eukaryotes 5mC plays a major role in many different processes including genomic imprinting, DNA repair, response to stress and the environment, regulation of gene expression and immune response [133,[136][137][138][139]. The AT-rich Plasmodium genome [1] represents an obstacle for mass spectrometry-based methods to detect 5mC [140,141] and early analyses did not detect it [140].…”