Original Article Tumour necrosis factor-α (TNF-α) and miRNA expression in frontal and temporal neocortex in Alzheimer’s disease and the effect of TNF-α on miRNA expression in vitro
Doris Culpan, Patrick G Kehoe and Seth Love
Dementia Research Group, School of Clinical Sciences, University of Bristol, John James Buildings, Frenchay Hospital, Frenchay, Bristol, BS16 1LE, United Kingdom
Received January 11, 2011; accepted March 21, 2011; Epub March 25, 2011; published May 15, 2011
Abstract: Micro-RNAs (miRNAs) are short non-coding RNAs capable of regulating gene expression at the translational level. A number of studies have suggested that the expression of several miRNAs is changed in AD. The pro-inflammatory cytokine tumour necrosis factor-α (TNF-α) is increased in serum and CSF in AD. We measured the expression of TNFA and several AD candidate gene-associated miRNAs (let7a/b, miR-128a/b, miR-27a/b, miR-155) in frontal and temporal neocortex from AD and control brains. The expression of these miRNAs was also measured after incubating non-differentiated (NDC) and retinoic acid -differentiated (DC) SH-SY5Y neuroblastoma cells with TNF-α. TNFA expression was similar in AD and control brains but miR- 128a/b levels were significantly reduced in the temporal cortex and miR-128b in the frontal cortex in AD. MiRNA levels did not correlate with TNFA expression in brain tissue but exposure of NDC and DC SH-SY5Y cells to TNF-α caused a variable dose- dependent response in the level of some of the miRNAs studied. Our brain tissue findings argue against a role for TNF-α in influencing the expression of these miRNAs in AD. (IJMEG1101001).
Address all correspondence to: Doris Culpan Dementia Research Group, School of Clinical Sciences University of Bristol, John James Building, Frenchay Hospital Frenchay, Bristol, BS16 1LE, United Kingdom Tel: 0117 3403068 Fax: 0117 957 3955 E-mail: Doris.Culpan@bristol.ac.uk