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Mol Neurobiol. 2018 Dec;55(12):9089-9099. doi: 10.1007/s12035-018-1047-3. Epub 2018 Apr 10.

MiR-34a Regulates Axonal Growth of Dorsal Root Ganglia Neurons by Targeting FOXP2 and VAT1 in Postnatal and Adult Mouse.

Author information

1
Department of Neurology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202, USA.
2
Department of Neurolgoy, Xuanwu Hospital, Capital Medical University, Beijing, China.
3
Department of Physics Oakland University, Rochester, MI, 48309, USA.
4
Department of Neurology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202, USA. zhazh@neuro.hfh.edu.

Abstract

Hyperglycemia impairs nerve fibers of dorsal root ganglia (DRG) neurons, leading to diabetic peripheral neuropathy (DPN). However, the molecular mechanisms underlying DPN are not fully understood. Using a mouse model of type II diabetes (db/db mouse), we found that microRNA-34a (miR-34a) was over-expressed in DRG, sciatic nerve, and foot pad tissues of db/db mice. In vitro, high glucose significantly upregulated miR-34a in postnatal and adult DRG neurons, which was associated with inhibition of axonal growth. Overexpression and attenuation of miR-34a in postnatal and adult DRG neurons suppressed and promoted, respectively, axonal growth. Bioinformatic analysis suggested that miR-34a putatively targets forkhead box protein P2 (FOXP2) and vesicle amine transport 1 (VAT1), which were decreased in diabetic tissues and in cultured DRG neurons under high glucose conditions. Dual-luciferase assay showed that miR-34a downregulated FOXP2 and VAT1 expression by targeting their 3' UTR. Gain-of- and loss-of-function analysis showed an inverse relation between augmentation of miR-34a and reduction of FOXP2 and VAT1 proteins in postnatal and adult DRG neurons. Knockdown of FOXP2 and VAT1 reduced axonal growth. Together, these findings suggest that miR-34a and its target genes of FOXP2 and VAT1 are involved in DRG neuron damage under hyperglycemia.

KEYWORDS:

Axon growth; Neuron; Peripheral neuropathy; miR-34a

PMID:
29637443
PMCID:
PMC6179937
[Available on 2018-12-01]
DOI:
10.1007/s12035-018-1047-3

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