MilliporeSigma
  • Home
  • Search Results
  • Dysregulation of miR-34a links neuronal development to genetic risk factors for bipolar disorder.

Dysregulation of miR-34a links neuronal development to genetic risk factors for bipolar disorder.

Molecular psychiatry (2015-01-28)
S Bavamian, N Mellios, J Lalonde, D M Fass, J Wang, S D Sheridan, J M Madison, Fen Zhou, E H Rueckert, D Barker, R H Perlis, M Sur, S J Haggarty
ABSTRACT

Bipolar disorder (BD) is a heritable neuropsychiatric disorder with largely unknown pathogenesis. Given their prominent role in brain function and disease, we hypothesized that microRNAs (miRNAs) might be of importance for BD. Here we show that levels of miR-34a, which is predicted to target multiple genes implicated as genetic risk factors for BD, are increased in postmortem cerebellar tissue from BD patients, as well as in BD patient-derived neuronal cultures generated by reprogramming of human fibroblasts into induced neurons or into induced pluripotent stem cells (iPSCs) subsequently differentiated into neurons. Of the predicted miR-34a targets, we validated the BD risk genes ankyrin-3 (ANK3) and voltage-dependent L-type calcium channel subunit beta-3 (CACNB3) as direct miR-34a targets. Using human iPSC-derived neuronal progenitor cells, we further show that enhancement of miR-34a expression impairs neuronal differentiation, expression of synaptic proteins and neuronal morphology, whereas reducing endogenous miR-34a expression enhances dendritic elaboration. Taken together, we propose that miR-34a serves as a critical link between multiple etiological factors for BD and its pathogenesis through the regulation of a molecular network essential for neuronal development and synaptogenesis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium dodecyl sulfate, ≥99.0% (GC), dust-free pellets
Sigma-Aldrich
L-Ascorbic acid, FCC, FG
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC), free-flowing, Redi-Dri
Supelco
Sodium dodecyl sulfate, dust-free pellets, suitable for electrophoresis, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
Bicinchoninic acid disodium salt hydrate, ≥98% (HPLC)
Sigma-Aldrich
L-Ascorbic acid, suitable for cell culture, suitable for plant cell culture, ≥98%
Sigma-Aldrich
L-Ascorbic acid, meets USP testing specifications
Sigma-Aldrich
L-Ascorbic acid, powder, suitable for cell culture, γ-irradiated
Sigma-Aldrich
Monoclonal Anti-Synaptophysin antibody produced in mouse, clone SVP-38, ascites fluid
Sigma-Aldrich
Sodium dodecyl sulfate, ReagentPlus®, ≥98.5% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
Sigma-Aldrich
L-Ascorbic acid, BioXtra, ≥99.0%, crystalline
Sigma-Aldrich
Sodium dodecyl sulfate, BioXtra, ≥99.0% (GC)
Sigma-Aldrich
2-Propylpentanoic acid
Sigma-Aldrich
L-Ascorbic acid, suitable for plant cell culture
Sigma-Aldrich
Sodium dodecyl sulfate, 92.5-100.5% based on total alkyl sulfate content basis
Sigma-Aldrich
L-Ascorbic acid, reagent grade, crystalline
Sigma-Aldrich
Puromycin dihydrochloride from Streptomyces alboniger, ≥98% (HPLC), powder
Sigma-Aldrich
L-Ascorbic acid, reagent grade
Sigma-Aldrich
L-Ascorbic acid, 99%
Sigma-Aldrich
L-Ascorbic acid, puriss. p.a., ≥99.0% (RT)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥90%
Sigma-Aldrich
L-Ascorbic acid, BioUltra, ≥99.5% (RT)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, tested according to NF, mixture of sodium alkyl sulfates consisting mainly of sodium dodecyl sulfate
Sigma-Aldrich
Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
L-Ascorbic acid, puriss. p.a., ACS reagent, reag. ISO, Ph. Eur., 99.7-100.5% (oxidimetric)
Sigma-Aldrich
L-Ascorbic acid, ACS reagent, ≥99%
Sigma-Aldrich
Sodium dodecyl sulfate, ACS reagent, ≥99.0%
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture