Transcriptional and Epigenetic Regulation in Injury-Mediated Neuronal Dendritic Plasticity

Abstract

Injury to the nervous system induces localized damage in neural structures and neuronal death through the primary insult, as well as delayed atrophy and impaired plasticity of the delicate dendritic fields necessary for interneuronal communication. Excitotoxicity and other secondary biochemical events contribute to morphological changes in neurons following injury. Evidence suggests that various transcription factors are involved in the dendritic response to injury and potential therapies. Transcription factors play critical roles in the intracellular regulation of neuronal morphological plasticity and dendritic growth and patterning. Mounting evidence supports a crucial role for epigenetic modifications via histone deacetylases, histone acetyltransferases, and DNA methyltransferases that modify gene expression in neuronal injury and repair processes. Gene regulation through epigenetic modification is of great interest in neurotrauma research, and an early picture is beginning to emerge concerning how injury triggers intracellular events that modulate such responses. This review provides an overview of injury-mediated influences on transcriptional regulation through epigenetic modification, the intracellular processes involved in the morphological consequences of such changes, and potential approaches to the therapeutic manipulation of neuronal epigenetics for regulating gene expression to facilitate growth and signaling through dendritic arborization following injury.

Targeting phosphodiesterase 4 as a potential therapeutic strategy for enhancing neuroplasticity following ischemic stroke

“…Neuroplasticity may also occur in various practices in our daily life, for example, when we try to learn a new skill or memorize a new information, persistent functional changes keep happening in our brain 25 . It may also occur under the condition of compensation for neural injury 26 .…”

The Protein Acetylation after Traumatic Spinal Cord Injury: Mechanisms and Therapeutic Opportunities

“…A variety of diseases arising from inflammation, internal or external damages, alter epigenetic regulations, including DNA methylation, histone methylation, and histone acetylation. Evidence has demonstrated that epigenetic regulations play an essential role in mediating spinal cord plasticity and neuronal differentiation during SCI [17][18][19]. The epigenetic modification processes are associated with mechanisms that underlie the repair and therapy of SCI.…”

Epigenetic processes associated with neonatal spinal transection

“…To date, most of the literature on adult spinal cord plasticity has focused on injury outcomes (Wang, Li, et al, 2016;), pain (Jiang et al, 2017;Zhao et al, 2017), or disease (Martin & Wong, 2013;Miranpuri et al, 2017), with limited data providing a developmental profile of epigenetic mechanisms associated with neurobehavioral plasticity in the spinal cord. Understanding these mechanisms may shed insight on why the spinal cord is most responsive to environmental input during early development, as epigenomics is a known moderator of environmental input and future behavioral states, including increased disease states (e.g., Cheng et al, 2022;McGowan et al, 2009;Roth et al, 2009;Szyf, 2009;Weaver et al, 2004).…”