Hyperexcitability precedes motoneuron loss in the Smn2B/- mouse model of spinal muscular atrophy.

Journal of Neurophysiology
K A QuinlanC J DiDonato

Abstract

Spinal motoneuron dysfunction and loss are pathological hallmarks of the neuromuscular disease spinal muscular atrophy (SMA). Changes in motoneuron physiological function precede cell death, but how these alterations vary with disease severity and motoneuron maturational state is unknown. To address this question, we assessed the electrophysiology and morphology of spinal motoneurons of presymptomatic Smn2B/- mice older than 1 wk of age and tracked the timing of motor unit loss in this model using motor unit number estimation (MUNE). In contrast to other commonly used SMA mouse models, Smn2B/- mice exhibit more typical postnatal development until postnatal day (P)11 or 12 and have longer survival (~3 wk of age). We demonstrate that Smn2B/- motoneuron hyperexcitability, marked by hyperpolarization of the threshold voltage for action potential firing, was present at P9-10 and preceded the loss of motor units. Using MUNE studies, we determined that motor unit loss in this mouse model occurred 2 wk after birth. Smn2B/- motoneurons were also larger in size, which may reflect compensatory changes taking place during postnatal development. This work suggests that motoneuron hyperexcitability, marked by a reduced threshold for action p...Continue Reading

References

Nov 1, 1973·The Journal of Physiology·R E BurkeF E Zajac
May 1, 1965·Journal of Neurophysiology·E HennemanD O Carpenter
Apr 1, 1965·Animal Behaviour·W M Fox
Jun 1, 1980·Journal of Neurophysiology·P C Schwindt, W E Crill
Apr 1, 1996·Neurobiology of Disease·T O Crawford, C A Pardo
Aug 1, 1997·Human Molecular Genetics·D D CoovertA H Burghes
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·B SchrankM Sendtner
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·C L LorsonB Wirth
Dec 30, 1999·Nature Genetics·H M Hsieh-LiH Li
May 3, 2000·The European Journal of Neuroscience·K P CarlinR M Brownstone
Jun 18, 2002·Current Opinion in Cell Biology·Sergey PaushkinGideon Dreyfuss
Nov 21, 2002·Trends in Cell Biology·Gunter MeisterUtz Fischer
Jun 5, 2003·Human Molecular Genetics·Yick Bun ChanMarcel van den Heuvel
Sep 4, 2003·The Journal of Cell Biology·Michelle L McWhorterChristine E Beattie
Oct 3, 2003·Journal of Neurophysiology·Jason J KuoAlfons B A Kroese
Aug 23, 2005·Brain Research. Brain Research Reviews·Livia CarrascalPedro A Nunez-Abades
Jun 9, 2006·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Steve Vucic, Matthew C Kiernan
Mar 14, 2007·The Journal of Cell Biology·T K RajendraA Gregory Matera
Sep 1, 2007·Journal of Child Neurology·Aloicia Schmid, Christine J DiDonato
Jun 24, 2008·Lancet·Mitchell R Lunn, Ching H Wang
Sep 23, 2008·The Journal of Comparative Neurology·Julien Amendola, Jacques Durand
Dec 23, 2008·Nature·Allison D EbertClive N Svendsen
Jul 9, 2009·Nature Reviews. Neuroscience·Arthur H M Burghes, Christine E Beattie

❮ Previous
Next ❯

Citations

Apr 10, 2020·Frontiers in Cellular Neuroscience·Preston R SteeleKatharina A Quinlan

❮ Previous
Next ❯

Datasets Mentioned

BETA
MDA418685

Methods Mentioned

BETA
SMA
fluorescence microscopy
biopsies

Software Mentioned

WinFluor
MUNE
GraphPad Prism
Adobe Photoshop
SAS
Neurolucida
Neurolucida Explorer

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.