Aberrant brain microRNA target and miRISC gene expression in the anx/anx anorexia mouse model

Mercader, Josep M.; González, Juan R.; Lozano, Juan José; Bak, Mads; Kauppinen, Sakari; Sumoy, Lauro; Dierssen, Mara; Fernández‐Aranda, Fernando; Visa, Joana; Gratacòs, Mónica; Estivill, Xavier

doi:10.1016/j.gene.2012.01.057

Cited by 13 publications

(14 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increasing body of evidence shows that miRNAs play fundamental roles in neurogenesis, neuron survival, dendritic outgrowth and spine formation (29)(30)(31). Aberrant miRNA expression has also been linked to a variety of diseases, including several nervous system diseases (32)(33)(34). For example, miR-219 modulates N-methyl-D-aspartate (NMDA) receptor-mediated neurobehavioral dysfunction, which is implicated in schizophrenia and autism (35), and the expression of the sensory organ-specific miR-183 family has been shown to be altered following spinal nerve ligation (14).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Shen

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Chronic neuropathic pain is associated with global changes in gene expression in different areas of the nociceptive pathway. MicroRNAs (miRNAs) are small (~22 nt long) noncoding RNAs, which are able to regulate hundreds of different genes post-transcriptionally. The aim of this study was to determine the miRNA expression patterns in the different regions of the pain transmission pathway using a rat model of human neuropathic pain induced by bilateral sciatic nerve chronic constriction injury (bCCI). Using microarray analysis and quantitative reverse transcriptase-PCR, we observed a significant upregulation in miR-341 expression in the dorsal root ganglion (DRG), but not in the spinal dorsal horn (SDH), hippocampus or anterior cingulate cortex (ACC), in the rats with neuropathic pain compared to rats in the naïve and sham-operated groups. By contrast, the expression of miR-203, miR-181a-1 * and miR-541 * was significantly reduced in the SDH of rats with neuropathic pain. Our data indicate that miR-341 is upregulated in the DRG, whereas miR-203, miR-181a-1 * and miR-541 * are downregulated in the SDH under neuropathic pain conditions. Thus, the differential expression of miRNAs in the nervous system may play a role in the development of chronic pain. These observations may aid in the development of novel treatment methods for neuropathic pain, which may involve miRNA gene therapy in local regions. IntroductionNeuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting either the peripheral or central nervous system (1,2). Although pain has been investigated in depth for decades, neuropathic pain is still frequently under-treated (3), due to poor understanding of its pathophysiological and molecular mechanisms. Several regions of the nociceptive pathway, including the anterior cingulate cortex (ACC), hippocampus, spinal dorsal horn (SDH) and dorsal root ganglion (DRG), are involved in the development and maintenance of neuropathic pain (4-9). Several recent studies have shown that peripheral and central sensitization are associated with global changes in gene expression in different regions of the pain transmission pathway, and that these changes may be part of the mechanisms behind neuropathic pain (10-13). In order to elucidate the molecular mechanisms underlying neuropathic pain, it is essential to determine how gene expression patterns are altered by nerve injuries and how these alterations lead to the development and maintenance of chronic pain.miRNAs are a large class of short non-coding RNAs (~22 nt long), many of which are expressed either predominantly or exclusively in the nervous system (14-21). Furthermore, changes (either increases or decreases) in miRNA expression have been found in many disease states (22-24). Bilateral sciatic nerve chronic constriction injury (bCCI) is commonly used as a model for studying human neuropathic pain, in which chromic gut sutures are used to ligate each sciatic nerve. This model is characterized by long-lasting cold all...

show abstract

Section: Discussionmentioning

confidence: 99%

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Shen

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

show abstract

“…An aberrant expression of miRNA targets and RISC gene expression in the hypothalamus and cortex has been demonstrated in anx/anx mice [56]. Five RISC complex-related genes, including Dgcr8 , Ago2 , Fmr1 , Ddx6 and Pabpc1 , were upregulated in the hypothalamus of anx/anx mice [56].…”

Section: Roles Of Mirnas In Hypothalamic Regulationmentioning

confidence: 99%

MicroRNAs in the Hypothalamus

2013

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are short (∼22 nucleotides) non-coding ribonucleic acid (RNA) molecules that negatively regulate the expression of protein-coding genes. Posttranscriptional silencing of target genes by miRNA is initiated by binding to the 3′-untranslated regions of target mRNAs, resulting in specific cleavage and subsequent degradation of the mRNA or by translational repression resulting in specific inhibition of protein synthesis. An increasing amount of evidence shows that miRNAs control a large number of biological processes and there exists a direct link between miRNAs and disease. miRNA molecules are abundantly expressed in tissue-specific and regional patterns and have been suggested as potential biomarkers, disease modulators and drug targets. The central nervous system is a prominent site of miRNA expression. Within the brain, several miRNAs are expressed and/or enriched in the region of the hypothalamus and miRNAs have recently been shown to be important regulators of hypothalamic control functions. The aim of this review is to summarize some of the current knowledge regarding the expression and role of miRNAs in the hypothalamus.

show abstract

“…Particularly, the use of anx / anx mouse strain generated new theories on hypothalamic degeneration and inflammation that might explain some of the behavioral characteristics of AN [8]. On the other hand, molecular studies on AN are also providing insight into how diet and nutrition can alter gene expression [9], which may in turn increases the risk for AN.…”

Section: Introductionmentioning

confidence: 99%

Microbiota in anorexia nervosa: The triangle between bacterial species, metabolites and psychological tests

Borgo

Riva

Benetti³

et al. 2017

PLoS ONE

205

248

View full text Add to dashboard Cite

Anorexia nervosa (AN) is a psychiatric disease with devastating physical consequences, with a pathophysiological mechanism still to be elucidated. Metagenomic studies on anorexia nervosa have revealed profound gut microbiome perturbations as a possible environmental factor involved in the disease. In this study we performed a comprehensive analysis integrating data on gut microbiota with clinical, anthropometric and psychological traits to gain new insight in the pathophysiology of AN. Fifteen AN women were compared with fifteen age-, sex- and ethnicity-matched healthy controls. AN diet was characterized by a significant lower energy intake, but macronutrient analysis highlighted a restriction only in fats and carbohydrates consumption. Next generation sequencing showed that AN intestinal microbiota was significantly affected at every taxonomic level, showing a significant increase of Enterobacteriaceae, and of the archeon Methanobrevibacter smithii compared with healthy controls. On the contrary, the genera Roseburia, Ruminococcus and Clostridium, were depleted, in line with the observed reduction in AN of total short chain fatty acids, butyrate, and propionate. Butyrate concentrations inversely correlated with anxiety levels, whereas propionate directly correlated with insulin levels and with the relative abundance of Roseburia inulinivorans, a known propionate producer. BMI represented the best predictive value for gut dysbiosis and metabolic alterations, showing a negative correlation with Bacteroides uniformis (microbiota), with alanine aminotransferase (liver function), and with psychopathological scores (obsession-compulsion, anxiety, and depression), and a positive correlation with white blood cells count. In conclusion, our findings corroborate the hypothesis that the gut dysbiosis could take part in the AN neurobiology, in particular in sustaining the persistence of alterations that eventually result in relapses after renourishment and psychological therapy, but causality still needs to be proven.

show abstract

Aberrant brain microRNA target and miRISC gene expression in the anx/anx anorexia mouse model

Cited by 13 publications

References 65 publications

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

MicroRNAs in the Hypothalamus

Microbiota in anorexia nervosa: The triangle between bacterial species, metabolites and psychological tests

Contact Info

Product

Resources

About