News archives


OCTOBER - DECEMBER 17

JULY - SEPTEMBER 17

APRIL - JUNE 17

JANUARY - MARCH 17

OCTOBER - DECEMBER 16

JULY - SEPTEMBER 16

APRIL - JUNE 16

JANUARY - MARCH 16

OCTOBER - DECEMBER 15

JULY - SEPTEMBER 15

APRIL - JUNE 15

JANUARY - MARCH 15

OCTOBER - DECEMBER 14

JULY - SEPTEMBER 14

APRIL - JUNE 14

JANUARY - MARCH 14

OCTOBER - DECEMBER 13

JULY - SEPTEMBER 13

APRIL - JUNE 13

JANUARY - MARCH 13

OCTOBER - DECEMBER 12

JULY - SEPTEMBER 12

APRIL - JUNE 12

JANUARY - MARCH 12

OCTOBER - DECEMBER 11

JULY - SEPTEMBER 11

APRIL - JUNE 11

JANUARY - MARCH 11

OCTOBER - DECEMBER 10

JULY - SEPTEMBER 10

APRIL - JUNE 10

JANUARY - MARCH 10

OCTOBER - DECEMBER 09

JULY - SEPTEMBER 09

APRIL - JUNE 09

JANUARY - MARCH 09

OCTOBER - DECEMBER 08

JULY - SEPTEMBER 08

APRIL - JUNE 08

JANUARY - MARCH 08

OCTOBER - DECEMBER 07

JULY - SEPTEMBER 07

APRIL - JUNE 07

JANUARY - MARCH 07

 
  current news   Press   selected story    
     
  13 February 2015  
 
A neuroprotective role for microRNA mir-1000 mediated by limiting glutamate excitotoxicity
 
 




Authors
Pushpa Verma1,2, George J. Augustine 1,3-5, Mohamed-Raafet Ammar6, Ayumu Tashiro6 and Stephen M Cohen 1,2,7

1  Institute of Molecular and Cell Biology, 61 Biopolis Dr., Singapore 138673
2  Department of Biological Sciences, National University of Singapore
3  Duke-NUS Graduate Medical School, 8 College Road, Singapore, 169857
4  Center for Functional Connectomics, Korea Institute of Science and Technology, 39-1 Hawolgokdong,    Seongbukgu, Seoul, 136-791 Republic of Korea
5  Lee Kong Chian School of Medicine, Nanyang Technological University, 50 Nanyang Drive, Research    Techno Plaza, Singapore 637553 Singapore
6  Warwick-NTU Neuroscience Programme, School of Biological Sciences, Nanyang Technological    University, Singapore and School of Life Sciences, University of Warwick, Coventry, UK
7  Present address
   Department of Cellular and Molecular Medicine, University of Copenhagen, Blejdamsvej 3, Copenhagen    2200N, Denmark

Published online in Nature Neuroscience on 2nd February 2015.

Abstract
In recent years, microRNAs (miRNAs) have emerged as important regulators of homeostatic mechanisms. Evidence has begun to emerge for roles of microRNAs as regulators of synaptic signaling, specifically acting to control postsynaptic responsiveness during synaptic transmission. In this report, we provide evidence that miR-1000 acts presynaptically to regulate excitatory neurotransmitter, glutamate release at the synapse by controlling expression of the vesicular glutamate transporter (VGlut). Genetic deletion of miR-1000 leads to glutamatergic excitotoxicity, which causes early onset neuronal death, impaired movement and short lifespan. The seed-similar miR-137 regulates VGlut2 expression in mouse neurons. These conserved miRNAs share a neuroprotective function in the brains of flies and mice. Drosophila miR-1000 shows activity-dependent expression, which might serve as a mechanism to allow neuronal activity to fine-tune the strength of excitatory synaptic transmission.

Figure:

Figure Legend: Phenotypic characterization of miR-1000 mutants.

(a) Adult lifespan. KO1: miR-1000KO1 deletion mutant allele; KO2: miR-1000KO2 RMCE (Recombinase- mediated cassette exchange) deletion mutant allele with mini-white removed; Rescue: flies homozygous for the RMCE allele with the miR-1000 reintroduced. Df: Df(3R)Exel6203, a deletion removing miR-1000. Control was yw. Analyzed using Kaplan-Meier statistics and the Mantel-Cox log rank test: p < 0.0001 comparing miR-1000KO11/miR-1000KO2, miR-1000KO1/Df and miR-1000KO2/Df with miR-1000KO1/+, miR-1000KO2/+ Df/+ and yw controls. The controls were not significantly different from each other. p < 0.0001 comparing rescue with miR-1000KO1/miR-1000KO2, miR-1000KO1/Df and miR-1000KO2/Df. N > 60 flies/genotype; rescue n = 104. 

(b)
Climbing assays show the percentage of flies that climbed >5 cm in a 30 cm column. Data represent at least 3 independent biological replicates (20 flies/batch, 2d and 10d age). Analyzed by ANOVA, Holm-Sidak multiple comparison test: p < 0.0001 mutants vs controls and rescue. Error bars: mean ± s.d.

(c)
Caspase3 positive cells in 2d and 10d old brains. Anti-Caspase3 (red) shows apoptotic cells. Anti-Dlg (green) shows brain morphology. Scale bar: 50 µm.


For more information on Stephen COHEN 's laboratory, please click here.