Where Environment Meets Cognition: A Focus on Two Developmental Intellectual Disability Disorders

Figure 4

Reestablishing a balanced epigenetic state to rescue the cognitive impairment in Down Syndrome (DS) and Fragile X Syndrome (FXS). Cartoon representation of a DS (left) and FXS (right) pyramidal neuron. In both syndromes alterations in synaptic plasticity, local protein synthesis, spine morphogenesis, and memory and learning contribute to the cognitive impairment. However the structural phenotype is distinct: DS neurons have large and stubby spines, while FXS neurons have long immature filopodia-like spines. Key genes involved in these pathways (e.g., APP, SYNJ1, TIAM1, and TTC3) are commonly deregulated due to epigenetic modifications at the chromatin level. The cartoon shows the repression of “memory” genes by DNA methylation (red circles) and H3K9 and H3K27 trimethylation (violet squares) in DS and FXS, with consequent chromatin compaction. Conversely, epigallocatechin gallate (EGCG) and Environmental Enrichment (EE) or directly epidrugs can reactivate the chromatin state at the level of “memory” gene by DNA hydroxymethylation (blue circles), H3K4 methylation (green triangles), and histone acetylation (yellow squares), rescuing the cognitive deficits.