microRNA Regulation of Synaptic Plasticity

Smalheiser, Neil R.; Lugli, Giovanni

doi:10.1007/s12017-009-8065-2

Cited by 114 publications

(84 citation statements)

References 48 publications

(70 reference statements)

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“…Furthermore, compelling evidence has demonstrated the substantial regulatory role of miRNAs in energy metabolism and liver functions (Poy et al 2004, Esau et al 2006, Plaisance et al 2006. miRNAs are also implicated in neuronal development, dendritic spine formation, synaptic plasticity (Vo et al 2005, Schratt et al 2006, Smalheiser & Lugli 2009, as well as in the regulation of signaling pathways (Inui et al 2010). However, little is known concerning the expression profile of miRNAs in the hypothalamus and whether leptin can modulate it in early life.…”

Section: Introductionmentioning

confidence: 99%

Early leptin blockade predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs

Benoît¹,

Ould-Hamouda²,

Crépin³

et al. 2013

Journal of Endocrinology

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Perinatal leptin impairment has long-term consequences on energy homeostasis leading to body weight gain. The underlying mechanisms are still not clearly established. We aimed to analyze the long-term effects of early leptin blockade. In this study, newborn rats received daily injection of a pegylated rat leptin antagonist (pRLA) or saline from day 2 (d2) to d13 and then body weight gain, insulin/leptin sensitivity, and expression profile of microRNAs (miRNAs) at the hypothalamic level were determined at d28, d90, or d153 (following 1 month of high-fat diet (HFD) challenge). We show that pRLA treatment predisposes rats to overweight and promotes leptin/insulin resistance in both hypothalamus and liver at adulthood. pRLA treatment also modifies the hypothalamic miRNA expression profile at d28 leading to the upregulation of 34 miRNAs and the downregulation of four miRNAs. For quantitative RT-PCR confirmation, we show the upregulation of rno-miR-10a at d28 and rno-miR-200a, rno-miR-409-5p, and rno-miR-125a-3p following HFD challenge. Finally, pRLA treatment modifies the expression of genes involved in energy homeostasis control such as UCPs and AdipoRs. In pRLA rat muscle, Ucp2/3 and Adipor1/r2 are upregulated at d90. In liver, pRLA treatment upregulates Adipor1/r2 following HFD challenge. These genes are known to be involved in insulin resistance and type 2 diabetes. In conclusion, we demonstrate that the impairment of leptin action in early life promotes insulin/leptin resistance and modifies the hypothalamic miRNA expression pattern in adulthood, and finally, this study highlights the potential link between hypothalamic miRNA expression pattern and insulin/leptin responsiveness.

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Section: Introductionmentioning

confidence: 99%

Early leptin blockade predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs

Benoît¹,

Ould-Hamouda²,

Crépin³

et al. 2013

Journal of Endocrinology

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“…It has been considered that microRNAS (miRNAs), which are small, noncoding RNA molecules, play important roles as key modulators of post-transcriptional gene expression (Smalheiser and Lugli, 2009). In addition, several lines of evidence suggest that miRNAs are closely related to the regulation of synaptic plasticity (John et al, 2004;Vo et al, 2005;Wu and Xie, 2006;Klein et al, 2007;Nomura et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Change in MicroRNAs Associated with Neuronal Adaptive Responses in the Nucleus Accumbens under Neuropathic Pain

Imai

Saeki²,

Yanase³

et al. 2011

J. Neurosci.

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Neuropathic pain is the most difficult type of pain to control, and patients lose their motivation for the purposive pursuit with a decrease in their quality of life. Using a functional magnetic resonance imaging analysis, we demonstrated that blood oxygenation level-dependent signal intensity was increased in the ipsilateral nucleus accumbens (N.Acc.) following peripheral nerve injury. microRNAs are small, noncoding RNA molecules that direct the post-transcriptional suppression of gene expression, and play an important role in regulating synaptic plasticity. In this study, we found that sciatic nerve ligation induced a drastic decrease in the expression of miR200b and miR429 in N.Acc. neurons. The expression of DNA methyltransferase 3a (DNMT3a), which is the one of the predicted targets of miR200b/429, was significantly increased in the limbic forebrain including N.Acc. at 7 d after sciatic nerve ligation. Double-immunolabeling with antibodies specific to DNMT3a and NR1 showed that DNMT3a-immunoreactivity in the N.Acc. was located in NR1-labeled neurons, indicating that increased DNMT3a proteins were dominantly expressed in postsynaptic neurons in the N.Acc. area under a neuropathic pain-like state. The results of these analyses provide new insight into an epigenetic modification that is accompanied by a dramatic decrease in miR200b and miR429 along with the dysfunction of "mesolimbic motivation/valuation circuitry" under a neuropathic pain-like state. These phenomena may result in an increase in DNMT3a in neurons of the N.Acc. under neuropathic pain, which leads to the long-term transcription-silencing of several genes.

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“…miRNAs are active within the CNS as well, where they regulate neuroplasticity through mediators such as cAMP responsive element binding protein (CREB1), methyl CpG binding protein 2 (MeCP2) and FMRP [43,44,45,46]. miRNAs are also found within the dendrites where they regulate local protein translation [47,48]. Therefore, miRNAs, if altered in DS, could impact synaptic function in the dendrites and contribute to the abnormal physiological properties of DS neurons [30,31,32].…”

Section: Introductionmentioning

confidence: 99%

Abnormal MicroRNA Expression in Ts65Dn Hippocampus and Whole Blood: Contributions to Down Syndrome Phenotypes

et al. 2011

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Down syndrome (DS; trisomy 21) is one of the most common genetic causes of intellectual disability, which is attributed to triplication of genes located on chromosome 21. Elevated levels of several microRNAs (miRNAs) located on chromosome 21 have been reported in human DS heart and brain tissues. The Ts65Dn mouse model is the most investigated DS model with a triplicated segment of mouse chromosome 16 harboring genes orthologous to those on human chromosome 21. Using ABI TaqMan miRNA arrays, we found a set of miRNAs that were significantly up- or downregulated in the Ts65Dn hippocampus compared to euploid controls. Furthermore, miR-155 and miR-802 showed significant overexpression in the Ts65Dn hippocampus, thereby confirming results of previous studies. Interestingly, miR-155 and miR-802 were also overexpressed in the Ts65Dn whole blood but not in lung tissue. We also found overexpression of the miR-155 precursors, pri- and pre-miR-155 derived from the miR-155 host gene, known as B cell integration cluster, suggesting enhanced biogenesis of miR-155. Bioinformatic analysis revealed that neurodevelopment, differentiation of neuroglia, apoptosis, cell cycle, and signaling pathways including ERK/MAPK, protein kinase C, phosphatidylinositol 3-kinase, m-TOR and calcium signaling are likely targets of these miRNAs. We selected some of these potential gene targets and found downregulation of mRNA encoding Ship1, Mecp2 and Ezh2 in Ts65Dn hippocampus. Interestingly, the miR-155 target gene Ship1 (inositol phosphatase) was also downregulated in Ts65Dn whole blood but not in lung tissue. Our findings provide insights into miRNA-mediated gene regulation in Ts65Dn mice and their potential contribution to impaired hippocampal synaptic plasticity and neurogenesis, as well as hemopoietic abnormalities observed in DS.

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microRNA Regulation of Synaptic Plasticity

Cited by 114 publications

References 48 publications

Early leptin blockade predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs

Early leptin blockade predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs

Change in MicroRNAs Associated with Neuronal Adaptive Responses in the Nucleus Accumbens under Neuropathic Pain

Abnormal MicroRNA Expression in Ts65Dn Hippocampus and Whole Blood: Contributions to Down Syndrome Phenotypes

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