Type

Journal Article

Authors

David C Henshall
Raymond L Stallings
Roger P Simon
Robert Meller
Donncha O'Brien
Michael Farrell
Norman Delanty
Catherine Moran
Zuzanna Michalak
Takanori Sano
and 5 others

Subjects

Biochemistry

Topics
computational biology humans middle aged animals micrornas female genetics hippocampus dead box rna helicases mice sclerosis ribonuclease iii epilepsy temporal lobe male dicer1 protein human adult dicer1 protein mouse pathology

Reduced mature microRNA levels in association with dicer loss in human temporal lobe epilepsy with hippocampal sclerosis. (2011)

Abstract Hippocampal sclerosis (HS) is a common pathological finding in patients with temporal lobe epilepsy (TLE) and is associated with altered expression of genes controlling neuronal excitability, glial function, neuroinflammation and cell death. MicroRNAs (miRNAs), a class of small non-coding RNAs, function as post-transcriptional regulators of gene expression and are critical for normal brain development and function. Production of mature miRNAs requires Dicer, an RNAase III, loss of which has been shown to cause neuronal and glial dysfunction, seizures, and neurodegeneration. Here we investigated miRNA biogenesis in hippocampal and neocortical resection specimens from pharmacoresistant TLE patients and autopsy controls. Western blot analysis revealed protein levels of Dicer were significantly lower in certain TLE patients with HS. Dicer levels were also reduced in the hippocampus of mice subject to experimentally-induced epilepsy. To determine if Dicer loss was associated with altered miRNA processing, we profiled levels of 380 mature miRNAs in control and TLE-HS samples. Expression of nearly 200 miRNAs was detected in control human hippocampus. In TLE-HS samples there was a large-scale reduction of miRNA expression, with 51% expressed at lower levels and a further 24% not detectable. Primary transcript (pri-miRNAs) expression levels for several tested miRNAs were not different between control and TLE-HS samples. These findings suggest loss of Dicer and failure of mature miRNA expression may be a feature of the pathophysiology of HS in patients with TLE.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David C Henshall, Raymond L Stallings, Roger P Simon, Robert Meller, Donncha O'Brien, Michael Farrell, Norman Delanty, Catherine Moran, Zuzanna Michalak, Takanori Sano and 5 others

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Raymond L Stallings
Royal College of Surgeons in Ireland
Total Publications: 59
 
3
Donncha F O'Brien
Royal College of Surgeons in Ireland
Total Publications: 19
 
4
Michael A Farrell
Royal College of Surgeons in Ireland
Total Publications: 43
 
5
Norman Delanty
Royal College of Surgeons in Ireland
Total Publications: 49
 
6
Zuzanna Michalak
Royal College of Surgeons in Ireland
Total Publications: 5