Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene that controls nerve conduction velocity linked to multiple sclerosis

13.08.2014

Evidence found in both human multiple sclerosis patients and experimental mouse models, according to research published in the American Journal of Pathology

A new study published in The American Journal of Pathology identifies a novel gene that controls nerve conduction velocity. Investigators report that even minor reductions in conduction velocity may aggravate disease in multiple sclerosis (MS) patients and in mice bred for the MS-like condition experimental autoimmune encephalomyelitis (EAE).

A strong tool for investigating the pathophysiology of a complex disease is the identification of underlying genetic controls. Multiple genes have been implicated as contributing to the risk of developing MS. Unlike studies that have focused on genetic regulators of inflammation, autoimmunity, demyelination, and neurodegeneration in MS, this study focused on nerve conduction velocity. Investigators found that polymorphisms of the inositol polyphosphate-4-phosphatase, type II (Inpp4b) gene affect the speed of nerve conduction in both mice with EAE and humans with MS.

"Impairment of nerve conduction is a common feature in neurodegenerative and neuroinflammatory diseases such as MS. Measurement of evoked potentials (whether visual, motor, or sensory) is widely used for diagnosis and recently also as a prognostic marker for MS," says lead investigator Saleh M. Ibrahim, MD, PhD, of the Department of Dermatology, Venereology, and Allergology of the University of Lubeck (Germany).

... more about:
»Elsevier »Health »MS »amino »controls »polymorphisms »sclerosis »strains

Using several genomic approaches, the investigators narrowed their search to the genetic region controlling the enzyme inositol-polyphosphate-4-phosphatase II (INPP4B), the product of which helps to regulate the phosphatidyl inositol signaling pathway. Enzymes in this family are involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival, and intracellular communication.

In one series of experiments, the researchers analyzed the genetic locus EAE31, which previously had been shown to control the latency of motor evoked potentials and clinical onset of EAE in mice. Using advanced techniques including congenic mapping, in silico haplotype analyses (computer simulations), and comparative genomics (from rats, mice and humans), they were able to "finemap" the focus to Inpp4b as the quantitative trait gene for EAE31.

When the investigators analyzed this region in eight different strains of mice, they found they could divide the strains into two groups based on differences in amino acid sequences. The strains with the longer-latency SJL/J allele had the two amino acids (arginine and proline), whereas those with the shorter-latency C57BL/10S allele had others (serine and histidine). "These data suggest that Inpp4b structural polymorphism is associated with the speed of neuronal conduction," comments Dr. Ibrahim.

In another experiment, the scientists compared motor conduction velocity in genetically modified mice with a mutant Inpp4b gene to that of control mice. The nerve conduction in this group was slower than in the control group.

Finally, the investigators studied INPP4B polymorphisms in MS patients. They looked at two cohorts: one from Spain (349 cases and 362 controls) and a second from Germany (562 cases and 3,314 controls). The association between the INPP4B polymorphisms and susceptibility to MS was statistically significant when the cohorts were pooled. However, although the Spanish cohort showed a strong association between INPP4B and MS, the association was weaker in the German cohort. "The exact reason for the diverging effect across these populations remains unresolved," states Dr. Ibrahim.

In an accompanying commentary, Hans Lassmann, MD, of the Center for Brain Research of the Medical University of Vienna (Austria) notes, "This study represents an interesting example of how minor changes in conduction velocity, which do not result in a clinical phenotype in control populations, may aggravate disease in conditions such as EAE or MS."

In other words, impaired nerve conduction may have a greater impact on those with MS compared to healthy individuals. Noting that the study reported no major loss of myelin in animals carrying the mutant allele, Dr. Lassmann comments that it is still unclear which neurobiological mechanisms underlie the INPP4B-associated impaired conduction. One suggestion is that INPP4B may be involved in calcium ion signaling within synapses, affecting neurotransmitter release.

Eileen Leahy | Eurek Alert!
Further information:
http://www.elsevier.com

Further reports about: Elsevier Health MS amino controls polymorphisms sclerosis strains

More articles from Health and Medicine:

nachricht Nanotubes are beacons in cancer-imaging technique
23.05.2016 | Rice University

nachricht More light on cancer
20.05.2016 | Lomonosov Moscow State University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Worldwide Success of Tyrolean Wastewater Treatment Technology

A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.

The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...

Im Focus: Computational high-throughput screening finds hard magnets containing less rare earth elements

Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.

The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...

Im Focus: Atomic precision: technologies for the next-but-one generation of microchips

In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.

In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...

Im Focus: Researchers demonstrate size quantization of Dirac fermions in graphene

Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices

Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.

Im Focus: Graphene: A quantum of current

When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene

In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

International expert meeting “Health Business Connect” in France

19.05.2016 | Event News

 
Latest News

11 million Euros for research into magnetic field sensors for medical diagnostics

27.05.2016 | Awards Funding

Fungi – a promising source of chemical diversity

27.05.2016 | Life Sciences

New Model of T Cell Activation

27.05.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>