Neuroplasticity Mediated by Altered Gene Expression

Department of Psychiatry and Center for Basic Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390-9070, USA.
Neuropsychopharmacology (Impact Factor: 7.83). 02/2008; 33(1):3-17. DOI: 10.1038/sj.npp.1301544
Source: PubMed

ABSTRACT Plasticity in the brain is important for learning and memory, and allows us to respond to changes in the environment. Furthermore, long periods of stress can lead to structural and excitatory changes associated with anxiety and depression that can be reversed by pharmacological treatment. Drugs of abuse can also cause long-lasting changes in reward-related circuits, resulting in addiction. Each of these forms of long-term plasticity in the brain requires changes in gene expression. Upon stimulation, second messenger pathways are activated that lead to an enhancement in transcription factor activity at gene promoters. This stimulation results in the expression of new growth factors, ion channels, structural molecules, and other proteins necessary to alter the neuronal circuit. With repeated stimulation, more permanent modifications to transcription factors and chromatin structure are made that result in either sensitization or desensitization of a circuit. Studies are beginning to uncover the molecular mechanisms that lead to these types of long-term changes in the brain. This review summarizes some of the major transcriptional mechanisms that are thought to underlie neuronal and behavioral plasticity.

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Available from: Colleen A Mcclung, Sep 03, 2015
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    • "Importantly, among the predicted targets of these miRNAs are genes of the MAP kinase pathway (eg, Map2k1; Map3k1), calcium-signaling-related genes (eg, Calml4, Camkk2), and Rho-signaling-related genes (eg, RhoGef, Rnd2) (Lewis et al, 2005). This finding is interesting in light of the role of miRNAs in neuronal development and neuroplasticity (McClung and Nestler, 2008) and their potential for serving as new therapeutic targets (Hansen and Obrietan, 2013). Indeed, several recent studies have demonstrated that miRNAs are both targets not only for disruption in mental illness (Kohen et al, 2014) but also for AD treatment action (Baudry et al, 2010; O'Connor et al, 2013). "
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    • "The regulation of gene expression during development is not only under the control of transcriptional machinery, but it is also affected by histone tail modifications (Hsieh and Gage, 2005; Wu and Sun, 2006) mediated by several histone-modifying enzymes (Kosztolanyi, 2011), including G9a (Ding et al., 2008; Rao et al., 2010). Chromatin modification, such as histone acetylation, has been implicated as a critical mechanism involved in the regulation of gene expression that may underlie longlasting changes in behavior (Barrett and Wood, 2008; McClung and Nestler, 2008; McQuown and Wood, 2010). Currently, very little is known about the specific histone acetyl transferase that regulates histone acetylation (Bekdash et al., 2013) implicated in ethanol effects within the developing hippocampus or neocortex. "
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