MicroRNAs are Necessary for BMP-7-induced Dendritic Growth in Cultured Rat Sympathetic Neurons

Abstract

Neuronal connectivity is dependent on size and shape of the dendritic arbor. However, mechanisms controlling dendritic arborization, especially in the peripheral nervous system, are not completely understood. Previous studies have shown that bone morphogenetic proteins (BMPs) are important initiators of dendritic growth in peripheral neurons. In this study, we examined the hypothesis that post-transcriptional regulation mediated by microRNAs (miRNAs) is necessary f or BMP-7 induced dendritic growth in these neurons. To examine the role of miRNAs in BMP-7-induced dendritic growth, microarray analyses was used to profile miRNA expression in cultured sympathetic neurons from the superior cervical ganglia of embryonic day 21 rat pups at 6 and 24 h after treatment with BMP-7 (50 ng/mL). Our data showed that BMP-7 significantly regulated the expression of 43 of the 762 miRNAs. Of the 43 miRNAs, 22 showed robust gene expression;14 were upregulated by BMP-7 and 8 were downregulated by BMP-7. The expression profile for miR-335, miR-664-1*, miR-21 and miR-23b was confirmed using qPCR analyses. Functional studies using morphometric analyses of d endritic growth in cultured sympathetic neurons transfected with miRNA mimics and inhibitors indicated that miR-664-1*, miR-23b and miR-21 regulated early stages of BMP-7 induced dendritic growth. In summary, our data provide evidence for miRNA-mediated post-transcriptional regulation as important downstream component of BMP-7 signaling during early stages of dendritic growth in sympathetic neurons.

Peripheral nerve injury: molecular pathophysiology and prospects for restorative treatment by means of cell transplantation: a literature review

“…Стан премоторних нейронів кори головного мозку і мотонейронів спинного мозку має важливе значення д ля успіх у відновного процес у при травмі рухових нервів [61][62][63][64]. Припускають, що ТПН зумовлює вибіркове ремоделювання кіркових синапсів, пов'язане з висхідною дегенерацією відрос тків чу тливих і ру хових нейронів та їх спорадичною загибеллю [65][66][67][68][69][70]. Як наслідокділянки кори, позбавлені звичайної аферентації, охоплюються мережевими впливами нейронних мереж сусідніх ділянок [70].…”

Crosstalk between Bone and Nerves within Bone

“…[ 205 ] The BMPs such as BMP‐7 also play critical roles in regulating the development of sympathetic neurons through mediating early stages of dendritic growth in sympathetic neurons. [ 206,207 ] In addition, they have been reported to regulate the expression and release of neurotransmitters or neuropeptides as well as the differentiation of neural cells. [ 208,209 ]…”

Signaling Pathways Regulating Axogenesis and Dendritogenesis in Sympathetic Neurons

“…Transcriptome and miRNome analyses have identified over 250 genes and over 40 microRNAs whose expression are altered in response to BMP-7 treatment in cultured sympathetic neurons during the period of dendritic growth initiation [132,133]. Of the genes, p75 NTR mRNA and protein are strongly upregulated by BMP-7 signaling in cultured SCG neurons.…”

“…However, p75 NTR ligands, interplay between neurotrophins and BMP in activating p75 NTR and downstream effectors of p75 NTR signaling responsible for dendritogenesis in sympathetic neurons still need to be elucidated. Of the microRNAs identified, three miRNAs -miR-21, miR-23b and miR-664-1* may regulate dendritic growth downstream of BMP-7 in sympathetic neurons in vitro [133]. Also, signaling pathways mediated by ubiquitin-proteasome system and by reactive oxygen species are suggested to be downstream of Smad signaling in sympathetic neurons in vitro with proteasome inhibitors and antioxidants inhibiting BMP-7 induced dendritic growth [135,136].…”