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!
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
Disrupted fat breakdown in the brain makes mice dumb
19.05.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.
Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...
22.05.2017 | Event News
17.05.2017 | Event News
16.05.2017 | Event News
22.05.2017 | Materials Sciences
22.05.2017 | Life Sciences
22.05.2017 | Physics and Astronomy