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MicroRNA function in neuronal development, plasticity and disease

Interdisziplinäres Zentrum für Neurowissenschaften, SFB488 Junior Group, Universität Heidelberg, and Institut für Neuroanatomie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 02/2008; 1779(8):471-8. DOI: 10.1016/j.bbagrm.2007.12.006
Source: PubMed

ABSTRACT

The development and function of the nervous system is orchestrated by a plethora of gene regulatory mechanisms. MicroRNAs (miRNAs), an abundant class of small non-coding RNAs, are emerging as important post-transcriptional regulators of gene expression in the brain. MiRNAs function at all stages of neuronal development, ranging from the initial specification of neuronal cell types to the formation and plasticity of synaptic connections between individual neurons. Moreover, links between miRNA dysfunction and neurological diseases become more and more apparent. The study of this novel layer of gene regulation therefore promises to enrich our knowledge of brain function and pathology.

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    • "In addition, miR-132 and EGR1 showed a significant positive correlation with ChAT-ir during the Braak stages, indicating that they may be involved in the functional changes in the NBM along the course of Alzheimer's disease. It should be noted that both miR-132 and EGR1 were found to show opposite effects in relation to Alzheimer's disease: they may both promote synaptic activity and plasticity (Fiore et al., 2008;Edbauer et al., 2010;Veyrac et al., 2014), and their 'upphase' of expression in the prefrontal cortex may thus play a key role in stimulating neuronal activity in early Alzheimer's disease stages. In contrast, they may also induce Alzheimer's disease pathology such as hyperphosphorylated tau (Min et al., 2010;Lu et al., 2011). "
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    ABSTRACT: The cholinergic nucleus basalis of Meynert, which is important for memory functions, shows neuronal activation ('up-phase') during the early stages of Alzheimer's disease and neurodegeneration ('down-phase') in later stages of Alzheimer's disease. MicroRNA-132 (miR-132) and the transcription factor early growth response-1 (EGR1) were proposed as possible candidate molecules regulating such an up-down activity pattern of the nucleus basalis of Meynert during the course of Alzheimer's disease, as they both show this up-down pattern of expression in the prefrontal cortex during the course of Alzheimer's disease. Not only do these two molecules stimulate synaptic activity and plasticity, they are also involved in Alzheimer's disease pathology and might, in addition, affect cholinergic function. In the nucleus basalis of Meynert, we investigated the expression of miR-132 and EGR1 along the entire course of Alzheimer's disease. Forty-nine post-mortem nucleus basalis of Meynert samples were studied, ranging from non-demented controls (Braak stage = 0) to late Alzheimer's disease patients (Braak stage = VI), and from clinical Reisberg scale 1 to 7. Each Braak stage contained seven samples, that were all well matched for confounding factors, i.e. age (range 58-91), sex, post-mortem delay, cerebrospinal fluid pH (as a measure for agonal state), APOE genotype, clock time of death, tissue fixation time, and tissue storage time. The alterations of these two molecules were studied over the course of Alzheimer's disease in relation to the expression of 4G8-stained amyloid-β, hyperphosphorylated tau stained by antibody AT8, neuronal fibrillary tangles and neuropil threads stained by silver, and in relation to alterations in choline acetyltransferase. We found that the expression of miR-132 and EGR1 in the nucleus basalis of Meynert was quite stable during the early stages of Alzheimer's disease and decreased significantly only during late Alzheimer's disease stages. In addition, miR-132 and EGR1 showed a significant positive correlation with choline acetyltransferase expression (r = 0.49, P < 0.001 and r = 0.61, P < 0.001), while choline acetyltransferase expression showed a significantly negative correlation with hyperphosphorylated tau (r = -0.33, P = 0.021) but no correlation with 4G8-stained amyloid-β. From the functional changes of miR-132 and EGR1 along the course of Alzheimer's disease we conclude: (i) that these two molecules may play a role in keeping the cholinergic function intact in early Alzheimer's disease stages; and (ii) that these molecules may contribute to the late neurodegeneration of this cholinergic nucleus.
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    • "Post-transcription interference by microRNAs (miRNAs) is another epigenetic mechanism and has been implied in neurogenesis and synaptic plasticity (Fiore et al., 2008). However, several representative miRNAs influential for neurogenesis and synaptic plasticity including miR9, miR124a, and miR132 did not significantly change their expression levels following EE (Kuzumaki et al., 2011). "
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    ABSTRACT: It has been half a century since brain volume enlargement was first reported in animals reared in an enriched environment (EE). As EE animals show improved memory task performance, exposure to EE has been a useful model system for studying the effects of experience on brain plasticity. We review EE-induced neural changes in the cerebral cortex and hippocampus focusing mainly on works published in the recent decade. The review is organized in three large domains of changes: anatomical, electrophysiological, and molecular changes. Finally, we discuss open issues and future outlook towards better understanding of EE-induced neural changes.
    Full-text · Article · Sep 2014 · Neuroscience
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    • "During the late embryonic stage, Dicer affects the survival and differentiation of cortical neural progenitor cells, leading to the deviant migration of cortical neurons 27. Ago, a part of the RNA-induced silencing complex 27, 28, also plays important roles in the CNS development. For example, neural tube closure is prevented in mice with Ago mutation 29. "
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    ABSTRACT: microRNAs (miRNAs) are a novel class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. miRNAs can modulate gene expression and thus play important roles in diverse neurobiological processes, such as cell differentiation, growth, proliferation and neural activity, as well as the pathogenic processes of spinal cord injury (SCI) like inflammation, oxidation, demyelination and apoptosis. Results from animal studies have revealed the temporal alterations in the expression of a large set of miRNAs following SCI in adult rats, and the expressional changes in miRNAs following SCI is bidirectional (increase or decrease). In addition, several miRNAs have distinct roles in prognosis of SCI (protective, detrimental and varied). Taken together, the existing evidence suggests that abnormal miRNA expression following SCI contributes to the pathogenesis of SCI, and miRNAs may become potential targets for the therapy of SCI.
    Preview · Article · Sep 2014 · International journal of biological sciences
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