MicroRNAs downregulated in neuropathic pain regulate MeCP2 and BDNF related to pain sensitivity

Autor: Melissa T. Manners, Yuzhen Tian, Zhaolan Zhou, Seena K. Ajit
Jazyk: angličtina
Předmět:
medicine.medical_specialty
Pathology
SNI
spared nerve injury
TrkB
tropomyosin receptor kinase B
congenital
hereditary
and neonatal diseases and abnormalities
QH301-705.5
RTT
Rett syndrome
BDNF
brain derived neurotrophic factor
Tropomyosin receptor kinase B
CFA
complete Freund’s adjuvant
Neuropathic pain
General Biochemistry
Genetics and Molecular Biology
MECP2
Downregulation and upregulation
Neurotrophic factors
−/Y
male Mecp2-null mouse
Internal medicine
MeCP2 T158A/Y
male MeCP2 T158A knock in mouse
Research article
mental disorders
medicine
T158A
threonine 158 conversion to alanine
Biology (General)
3′UTR
three prime untranslated region
MeCP2
miRNA
Brain-derived neurotrophic factor
ATF3
activating transcription factor 3
business.industry
L4/L5
4th or 5th lumbar vertebra
Chronic pain
Nerve injury
medicine.disease
nervous system diseases
DRG
dorsal root ganglia
MeCP2
methyl-CpG-binding protein 2
Endocrinology
BDNF
nervous system
medicine.symptom
business
+/Y
male wild-type littermate control for either MeCP2 T158A knock in mouse or Mecp2-null mouse
Zdroj: FEBS Open Bio
FEBS Open Bio, Vol 5, Iss 1, Pp 733-740 (2015)
ISSN: 2211-5463
DOI: 10.1016/j.fob.2015.08.010
Popis: Highlights • MeCP2 is upregulated in the dorsal root ganglia (DRG) from a spared nerve injury model of neuropathic pain. • miR-19a- and miR-301-mediated regulation of MeCP2 resulted in Bdnf alteration. • MeCP2 T158A mice have decreased mechanical sensitivity. • Bdnf is downregulated in the DRG in Mecp2-null mice and MeCP2 T158A mice.
Nerve injury induces chronic pain and dysregulation of microRNAs in dorsal root ganglia (DRG). Several downregulated microRNAs are predicted to target Mecp2. MECP2 mutations cause Rett syndrome and these patients report decreased pain perception. We confirmed MeCP2 upregulation in DRG following nerve injury and repression of MeCP2 by miRNAs in vitro. MeCP2 regulates brain-derived neurotrophic factor (BDNF) and downregulation of MeCP2 by microRNAs decreased Bdnf in vitro. MeCP2 T158A mice exhibited reduced mechanical sensitivity and Mecp2-null and MeCP2 T158A mice have decreased Bdnf in DRG. MeCP2-mediated regulation of Bdnf in the DRG could contribute to altered pain sensitivity.
Databáze: OpenAIRE
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