Therapeutic potential of N-acetyl-glucagon-like peptide-1 in primary motor neuron cultures derived from non-transgenic and SOD1-G93A ALS mice

Item Type:	Article
Title:	Therapeutic potential of N-acetyl-glucagon-like peptide-1 in primary motor neuron cultures derived from non-transgenic and SOD1-G93A ALS mice
Creators Name:	Sun, H. and Knippenberg, S. and Thau, N. and Ragancokova, D. and Koerner, S. and Huang, D. and Dengler, R. and Doehler, K. and Petri, S.
Abstract:	Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons (MN) in the motor cortex, brain stem, and spinal cord. In the present study, we established an ALS in vitro model of purified embryonic MNs, derived from non-transgenic and mutant SOD1-G93A transgenic mice, the most commonly used ALS animal model. MNs were cultured together with either non-transgenic or mutant SOD1-G93A astrocyte feeder layers. Cell viability following exposure to kainate as excitotoxic stimulus was assessed by immunocytochemistry and calcium imaging. We then examined the neuroprotective effects of N-acetyl-GLP-1(7-34) amide (N-ac-GLP-1), a long-acting, N-terminally acetylated, C-terminally truncated analog of glucagon-like peptide-1 (GLP-1). GLP-1 has initially been studied as a treatment for type II diabetes based on its function as insulin secretagogue. We detected neuroprotective effects of N-ac-GLP-1 in our in vitro system, which could be attributed to an attenuation of intracellular calcium transients, not only due to these antiexcitotoxic capacities but also with respect to the increasing knowledge about metabolic deficits in ALS which could be positively influenced by N-ac-GLP-1, this compound represents an interesting novel candidate for further in vivo evaluation in ALS.
Keywords:	Motor Neurons, Amyotrophic Lateral Sclerosis, Excitotoxicity, Glucagon-Like Peptide-1, Calcium Imaging, Animals, Mice
Source:	Cellular and Molecular Neurobiology
ISSN:	0272-4340
Publisher:	Springer
Volume:	33
Number:	3
Page Range:	347-357
Date:	April 2013
Official Publication:	https://doi.org/10.1007/s10571-012-9900-9
PubMed:	View item in PubMed

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