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!
Penn studies find promise for innovations in liquid biopsies
30.03.2017 | University of Pennsylvania School of Medicine
'On-off switch' brings researchers a step closer to potential HIV vaccine
30.03.2017 | University of Nebraska-Lincoln
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering