Marked changes in dendritic structure and spine density precede significant neuronal death in vulnerable cortical pyramidal neuron populations in the SOD1G93A mouse model of amyotrophic lateral sclerosis

Fogarty, Matthew J., Mu, Erica W. H., Noakes, Peter G., Lavidis, Nickolas A. and Bellingham, Mark C. (2016) Marked changes in dendritic structure and spine density precede significant neuronal death in vulnerable cortical pyramidal neuron populations in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Acta Neuropathologica Communications, 4 77: 1-21. doi:10.1186/s40478-016-0347-y


Author Fogarty, Matthew J.
Mu, Erica W. H.
Noakes, Peter G.
Lavidis, Nickolas A.
Bellingham, Mark C.
Title Marked changes in dendritic structure and spine density precede significant neuronal death in vulnerable cortical pyramidal neuron populations in the SOD1G93A mouse model of amyotrophic lateral sclerosis
Formatted title
Marked changes in dendritic structure and spine density precede significant neuronal death in vulnerable cortical pyramidal neuron populations in the SOD1G93A mouse model of amyotrophic lateral sclerosis
Journal name Acta Neuropathologica Communications   Check publisher's open access policy
ISSN 2051-5960
Publication date 2016-08-04
Year available 2016
Sub-type Article (original research)
DOI 10.1186/s40478-016-0347-y
Open Access Status DOI
Volume 4
Issue 77
Start page 1
End page 21
Total pages 21
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2017
Language eng
Formatted abstract
Amyotrophic lateral sclerosis (ALS) is characterised by the death of upper (corticospinal) and lower motor neurons (MNs) with progressive muscle weakness. This incurable disease is clinically heterogeneous and its aetiology remains unknown. Increased excitability of corticospinal MNs has been observed prior to symptoms in human and rodent studies. Increased excitability has been correlated with structural changes in neuronal dendritic arbors and spines for decades. Here, using a modified Golgi-Cox staining method, we have made the first longitudinal study examining the dendrites of pyramidal neurons from the motor cortex, medial pre-frontal cortex, somatosensory cortex and entorhinal cortex of hSOD1G93A (SOD1) mice compared to wild-type (WT) littermate controls at postnatal (P) days 8–15, 28–35, 65–75 and 120. Progressive decreases in dendritic length and spine density commencing at pre-symptomatic ages (P8-15 or P28-35) were observed in layer V pyramidal neurons within the motor cortex and medial pre-frontal cortex of SOD1 mice compared to WT mice. Spine loss without concurrent dendritic pathology was present in the pyramidal neurons of the somatosensory cortex from disease-onset (P65-75). Our results from the SOD1 model suggest that dendritic and dendritic spine changes foreshadow and underpin the neuromotor phenotypes present in ALS and may contribute to the varied cognitive, executive function and extra-motor symptoms commonly seen in ALS patients. Determining if these phenomena are compensatory or maladaptive may help explain differential susceptibility of neurons to degeneration in ALS.
Keyword Dendrite
Spine density
Cortex
Motor neuron disease
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
 
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Created: Tue, 09 Aug 2016, 11:44:10 EST by Dr Mark Bellingham on behalf of School of Biomedical Sciences