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: 7.05). 02/2008; 33(1):3-17. DOI: 10.1038/sj.npp.1301544
Source: PubMed


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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    • "Accumulating evidences have substantiated the role of brain plasticity as a molecular correlate of memory processes [9]. Activation of gene expression associated with neuronal and glial plasticity is considered to be a key mechanism underlying the enduring modification of neural networks required for the formation of memory [10] [11]. Amongst neuronal plasticity markers, brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, holds the most prominent place. "
    Dataset: 837012.v2

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    • "Brain cells depend on complex and highly regulated mechanisms to appropriately activate or silence gene programs in response to inputs from the environment. These events are controlled by activity-dependent signaling pathways that mediate gene expression by modifying the activity, localization, and/or expression of transcriptional-regulatory enzymes in combination with alterations in chromatin structure in the nucleus (McClung and Nestler, 2008). Therefore, "
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    ABSTRACT: Experience-dependent plasticity is the ability of brain circuits to undergo molecular, structural and functional changes as a function of neural activity. Neural activity continuously shapes our brain during all the stages of our life, from infancy through adulthood and beyond. Epigenetic modifications of histone proteins and DNA seem to be a leading molecular mechanism to modulate the transcriptional changes underlying the fine-tuning of synaptic connections and circuitry rewiring during activity-dependent plasticity. The recent discovery that cytosine methylation is an epigenetic mark particularly dynamic in brain cells has strongly increased the interest of neuroscientists in understanding the role of covalent modifications of DNA in activity-induced remodeling of neuronal circuits. Here, we provide an overview of the role of DNA methylation and hydroxylmethylation in brain plasticity both during adulthood, with emphasis on learning and memory related processes, and during postnatal development, focusing specifically on experience-dependent plasticity in the visual cortex.
    Frontiers in Cellular Neuroscience 09/2015; 9:331. DOI:10.3389/fncel.2015.00331 · 4.29 Impact Factor
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    • "Moreover, although the neuroadaptations that underlie locomotor sensitization to cocaine are thought to play an important role in the development of addiction (Robinson & Berridge, 1993; McClung & Nestler, 2008; Steketee & Kalivas, 2011), the impact of consuming a diet high in fat and/or sugar on drug-taking is less clear with remote histories of sugar or fat consumption having no effect, or enhancing cocaine self-administration, respectively (Vendruscolo , Gueye, Darnaudery, Ahmed, & Cador, 2010; Puhl, Cason, Wojnicki, Corwin, & Grigson, 2011). Future studies will be expanded to include drugs from diverse pharmacologic classes and to investigate the degree to which sex and dietary history (e.g., current vs. past, or continuous vs. intermittent consumption) impact the reinforcing effectiveness of drugs using intravenous selfadministration assays. "
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    ABSTRACT: Drug abuse and obesity are serious public health problems. Dopamine plays a central role in mediating the reinforcing effects of drugs and food. Prolonged use of drugs is known to alter the function and/or sensitivity of many neurotransmitter systems, including dopamine; however, the impact of consuming foods high in fat and/or sugar is less clear. These studies characterized the locomotor effects of acute and repeated cocaine in male and female C57BL/6J mice consuming 1 of 4 diets: (a) standard chow + water; (b) standard chow + 10% sucrose solution; (c) high-fat chow + water; or (d) high-fat chow + 10% sucrose solution. The acute locomotor effects of cocaine (3.2-32.0 mg/kg) were evaluated 4 weeks after initiating dietary conditions; the effects of repeated cocaine administration were evaluated after 5, 6, 7, and 12 weeks. During acute tests, mice consuming a diet high in fat and/or sucrose exhibited greater locomotor responses to cocaine than mice consuming standard chow and water, regardless of sex. Although diet-induced enhancements persisted across repeated cocaine testing, locomotor sensitization developed more rapidly in females drinking sucrose (and consuming either standard or high-fat chow) than in females consuming standard chow and water. In addition to providing evidence that consuming a diet high in fat and/or sugar enhances abuse-related effects of cocaine in ways that might increase vulnerability to abuse cocaine, these studies identified a potentially important sex-related difference in the interaction between nutrition and cocaine effects, with the impacts of sucrose consumption being greater in females than in males. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
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