NeuroLSD1: Splicing-Generated Epigenetic Enhancer of Neuroplasticity. Issue 1 (January 2017)

• Record Type: Journal Article
• Authors: Rusconi, Francesco; Grillo, Barbara; Toffolo, Emanuela; Mattevi, Andrea; Battaglioli, Elena
• Is Part Of: Trends in neurosciences. Volume 40:Issue 1(2017)
• Page Start: 28
• Page End: 38
• Publication Date: 2017-01
• Subjects: Neurology -- Periodicals; Neurophysiology -- Periodicals; Neurobiology -- Periodicals; 612.8
• DOI: 10.1016/j.tins.2016.11.002
• Languages: English
• ISSNs: 0166-2236

Abstract

Abstract : The acquisition and maintenance of the specific neuronal functions underlying learning, memory, and emotion require transduction of environmental stimuli into remodeling of neuronal circuitry. This process occurs via induction of plasticity-related transcriptional programs. The epigenetic enzyme lysine-specific demethylase-1 (LSD1), also known as lysine demethylase 1A (KDM1A), and its neurospecific splicing variant neuroLSD1 have been implicated in this process through an antagonistic mechanism. Specifically, LSD1/neuroLSD1 are involved in the negative and positive regulation of activity-evoked transcription of immediate early genes (IEGs) impacting memory formation and emotional behavior. Remarkably, the splicing process generating neuroLSD1 is homeostatically modulated by environmental contingencies, further implicating the LSD1/neuroLSD1 dual system as a modifier of information processing in the brain. Trends: Cell division and differentiation during neural development and cognitive processes in postnatal life share common molecular mechanisms. The mitogen-activated protein kinase pathway and its primary gene targets the immediate early genes (IEGs) regulate neuronal differentiation during development and subserve structural and synaptic plasticity in post-mitotic neurons. Epigenetic mechanisms convert environmental stimuli into long-lasting transcriptional modifications of plasticity genes, playing a fundamental role in maintaining experience-driven behavioral adaptations. The chromatin modifiers lysine-specific demethylase-1 (LSD1) and its neuron-restricted dominant-negative splicing isoform neuroLSD1 contribute to neuronal maturation and modulate experience-evoked transcription of IEGs in adulthood, revealing a common epigenetic drive for developmental and cognitive processes.