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Reduced VGLUT2 expression increases motor neuron viability in Sod1(G93A) mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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2010 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 37, no 1, 58-66 p.Article in journal (Refereed) Published
Abstract [en]

Glutamate-induced excitotoxicity has been suggested to influence pathogenesis in amyotrophic lateral sclerosis (ALS). Vesicular glutamate transporters (VGLUTs) are responsible for transport of glutamate into synaptic vesicles. Nerve terminals that envelop motor neurons in the spinal cord contain VGLUT2 and are likely responsible for most glutamate release on motor neurons. The role of VGLUT2 in ALS and its potential role to influence motor neuron survival have not previously been studied. Here, in a mouse model of ALS. we show that genetic reduction of VGLUT2 protein levels rescues motor neurons in the lumbar spinal cord and in the brainstem as well as neuromuscular junctions in tibialis anterior. Although the number of remaining motor neurons increased. neither disease onset nor life span was affected. We also show that the motor neuron subpopulation-specific markers calcitonin/calcitonin-related polypeptide alpha (Calca) and estrogen related receptor beta (ERR beta) respond in a similar way to reduced VGLUT2 as the whole motor neuron population suggesting that the rescued motor neurons are not of a particular motor unit type. Taken together, this suggests that reduced levels of VGLUT2 decrease motor neuron degeneration but do not prevent loss of motor neuron function in the SOD1(G93A) mouse model for ALS. (C) 2009 Elsevier Inc. All rights reserved

Place, publisher, year, edition, pages
2010. Vol. 37, no 1, 58-66 p.
Keyword [en]
ALS, Amyotrophic lateral sclerosis, Glutamate, Vglut2, Vesicular glutamate transporters, Excitotoxicity, Motor neuron, Neurodegeneration, Motor neuron subpopulations, Calca, Chondrolectin, Chodl, ERRb
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-127378DOI: 10.1016/j.nbd.2009.09.006ISI: 000272533000008OAI: oai:DiVA.org:uu-127378DiVA: diva2:329728
Available from: 2010-07-13 Created: 2010-07-13 Last updated: 2016-05-11Bibliographically approved
In thesis
1. Neural Control of Movement: Motor Neuron Subtypes, Proprioception and Recurrent Inhibition
Open this publication in new window or tab >>Neural Control of Movement: Motor Neuron Subtypes, Proprioception and Recurrent Inhibition
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Movement is central for life, and all animals depend on accurate regulation of movement for purposeful behavior. There is great diversity of movements, ranging between simple and vital breathing movements to minute and subtle movements of the face used to communicate emotions. Consequently, motor neurons, which are the only route of central nervous system output, are essential for all motor behaviors. To control the many motor behaviors expressed by an animal, motor neurons are exposed to a large number and variety of modulating synaptic inputs and have evolved into subtypes with specific functions. In this thesis, motor neuron subtypes and the synaptic input to motor neurons from Renshaw cells and Ia afferents have been studied. Novel molecular markers that identify subtypes of motor neurons are described. Three markers, Chodl, Calca and ERRβ, have been used to study the degeneration of subtypes of motor neurons in a mouse model of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Another marker, 5-ht1d, has been used to record the electrophysiological character of gamma motor neurons. In mice that lack 5-ht1d, motor neurons develop with reduced proprioceptive input. Remarkably, these mice had fewer foot faults than control animals when challenged to cross a narrow beam suggesting that the amplitude of monosynaptic proprioceptive input to motor neurons is not essential for motor coordination. In a final set of experiments, genetic removal of vesicular transport of neurotransmitter from Renshaw cells suggest that Renshaw cells are not integral for motor circuit function or motor behaviors. However, they are involved in the development of motor circuits in the spinal cord. Together, this thesis provides novel molecular tools for studies of motor neuron subtypes and novel data regarding the development and function of spinal motor circuits.


Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 61 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 660
motor neuron, proprioception, recurrent inhibition, molecular marker, Ia afferent, development, transgenic mice, Renshaw cell
National Category
Research subject
urn:nbn:se:uu:diva-147361 (URN)978-91-554-8043-1 (ISBN)
Public defence
2011-05-14, B21, BMC, Husargatan 3, Uppsala, 13:15 (English)
Available from: 2011-04-20 Created: 2011-02-25 Last updated: 2011-05-05Bibliographically approved

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Wootz, HannaWallen-Mackenzie, ÅsaKullander, Klas
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