Central and peripheral defects in motor units of the diaphragm of spinal muscular atrophy mice.

Neve, Anuja Vilas; Trüb, Judith; Saxena, Smita; Schümperli, Daniel (2016). Central and peripheral defects in motor units of the diaphragm of spinal muscular atrophy mice. Molecular and cellular neuroscience, 70, pp. 30-41. Elsevier 10.1016/j.mcn.2015.11.007

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Spinal muscular atrophy (SMA) is characterized by motoneuron loss and muscle weakness. However, the structural and functional deficits that lead to the impairment of the neuromuscular system remain poorly defined. By electron microscopy, we previously found that neuromuscular junctions (NMJs) and muscle fibres of the diaphragm are among the earliest affected structures in the severe mouse SMA model. Because of certain anatomical features, i.e. its thinness and its innervation from the cervical segments of the spinal cord, the diaphragm is particularly suitable to characterize both central and peripheral events. Here we show by immunohistochemistry that, at postnatal day 3, the cervical motoneurons of SMA mice receive less stimulatory synaptic inputs. Moreover, their mitochondria become less elongated which might represent an early stage of degeneration. The NMJs of the diaphragm of SMA mice show a loss of synaptic vesicles and active zones. Moreover, the partly innervated endplates lack S100 positive perisynaptic Schwann cells (PSCs). We also demonstrate the feasibility of comparing the proteomic composition between diaphragm regions enriched and poor in NMJs. By this approach we have identified two proteins that are significantly upregulated only in the NMJ-specific regions of SMA mice. These are apoptosis inducing factor 1 (AIFM1), a mitochondrial flavoprotein that initiates apoptosis in a caspase-independent pathway, and four and a half Lim domain protein 1 (FHL1), a regulator of skeletal muscle mass that has been implicated in several myopathies.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology
08 Faculty of Science > Department of Biology > Institute of Cell Biology > RNA

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Neve, Anuja Vilas; Trüb, Judith; Saxena, Smita and Schümperli, Daniel

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1044-7431

Publisher:

Elsevier

Language:

English

Submitter:

Daniel Schümperli

Date Deposited:

10 Mar 2016 16:40

Last Modified:

10 Mar 2016 16:40

Publisher DOI:

10.1016/j.mcn.2015.11.007

PubMed ID:

26621405

Uncontrolled Keywords:

Diaphragm; Motoneuron; Neuromuscular junction; Perisynaptic Schwann cell; Proteomics; Spinal muscular atrophy

BORIS DOI:

10.7892/boris.77082

URI:

https://boris.unibe.ch/id/eprint/77082

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