Massive elimination of neurons is a critical aspect of normal nervous system development but also represents a defining feature of neurodegenerative pathologies, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.
Although the molecular events that trigger neuronal death in each of these neurodegenerative diseases is distinct, the downstream apoptotic process through which neurons die in these pathologies are thought to share commonalities to each other, as well as to developmentally-regulated neuronal death.
Identifying genes that promote or prevent neuronal death would thus be an important step in understanding both developmentally-regulated neuronal death as well as the mechanisms underlying degenerative brain disorders. Scientists at Southern Methodist University, led by Professor and Chair of Biological Sciences Santosh D'Mello, have used RNA-Seq to conduct transcriptome profiling of gene expression changes in dying neurons.
This study, reported in the February 2015 issue of Experimental Biology and Medicine, utilized cultured cerebellar granule neurons, one of the most widely used models to study neuronal death. Other labs have used DNA microarray analysis to characterize gene expression changes in this model. However, microarray analysis is only capable of measuring the status of known transcripts, and expression of low-abundance mRNAs is often not detected by the hybridization-based approach.
While changes in the expression of several hundred genes were detected by microarray analyses, in the study by D'Mello and colleagues over 4,000 genes displayed significantly altered expression. Most affected were genes functioning in cell death and survival regulation, cell growth and proliferation and molecular transport. A large number of genes involved in nervous system development and function were also deregulated.
Analysis of signaling pathways that were affected pointed to changes in mitochondrial function and oxidative phosphorylation, consistent with a number of studies showing perturbations of these pathways in neurodegenerative disorders. A large number of genes previously not linked to developmentally-regulated neuronal death or neurodegenerative pathologies were identified.
"This is a first step in the identification of novel but important players regulating neuronal survival and death" said Dr. D'Mello. "Future studies will determine to what extent the novel genes identified in our study are involved in regulating neuronal death, including death associated with neurodegenerative disease."
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "D'Mello and colleagues have performed a transcriptomic study, utilizing RNA-Seq, to identify transcripts that are changed in expression in dying neurons. Utilizing this very sensitive technique they were able to demonstrate significant changes in the expression of over 4000 genes. This study opens the door to future studies on which of these many genes are functionally involved in normal neuronal death and that associated with various neurodegenerative disorders.
Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit http://www.
Dr. Santosh R. D'Mello | EurekAlert!
Inflammation Triggers Unsustainable Immune Response to Chronic Viral Infection
24.10.2016 | Universität Basel
Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
25.10.2016 | Earth Sciences
25.10.2016 | Power and Electrical Engineering
25.10.2016 | Process Engineering