The role of MeCP2 in regulating synaptic plasticity in the context of stress and depression
Date
2022
Authors
Sánchez-Lafuente, Carla L.
Kalynchuk, Lisa E.
Caruncho, Hector J.
Ausió, Juan
Journal Title
Journal ISSN
Volume Title
Publisher
Cells
Abstract
Methyl-CpG-binding protein 2 (MeCP2) is a transcriptional regulator that is highly abundant
in the brain. It binds to methylated genomic DNA to regulate a range of physiological functions
implicated in neuronal development and adult synaptic plasticity. MeCP2 has mainly been studied for
its role in neurodevelopmental disorders, but alterations in MeCP2 are also present in stress-related
disorders such as major depression. Impairments in both stress regulation and synaptic plasticity are
associated with depression, but the specific mechanisms underlying these changes have not been
identified. Here, we review the interplay between stress, synaptic plasticity, and MeCP2. We focus
our attention on the transcriptional regulation of important neuronal plasticity genes such as BDNF
and reelin (RELN). Moreover, we provide evidence from recent studies showing a link between
chronic stress-induced depressive symptoms and dysregulation of MeCP2 expression, underscoring
the role of this protein in stress-related pathology. We conclude that MeCP2 is a promising target for
the development of novel, more efficacious therapeutics for the treatment of stress-related disorders
such as depression.
Description
Keywords
methyl-CpG-binding protein 2 (MeCP2), epigenetics, reelin, depression, stress, synaptic plasticity, brain-derived neurotrophic factor (BDNF), transcriptional repression
Citation
Sánchez-Lafuente, C., Kalynchuk, L., Caruncho, H., & Ausió, J. (2022). “The role of MeCP2 in regulating synaptic plasticity in the context of stress and depression.” Cells, 11(4), 748. https://doi.org/10.3390/cells11040748