Lithium prevents excitotoxic cell death of motoneurons in organotypic slice cultures of spinal cord

Neuroscience
Jordi CalderóJosep E Esquerda

Abstract

Several studies have reported the neuroprotective effects of lithium (Li) suggesting its potential in the treatment of neurological disorders, among of them amyotrophic lateral sclerosis (ALS). Although the cause of motoneuron (MN) death in ALS remains unknown, there is evidence that glutamate-mediated excitotoxicity plays an important role. In the present study we used an organotypic culture system of chick embryo spinal cord to explore the presumptive neuroprotective effects of Li against kainate-induced excitotoxic MN death. We found that chronic treatment with Li prevented excitotoxic MN loss in a dose dependent manner and that this effect was mediated by the inhibition of glycogen synthase kinase-3beta (GSK-3beta) signaling pathway. This neuroprotective effect of Li was potentiated by a combined treatment with riluzole. Nevertheless, MNs rescued by Li displayed structural changes including accumulation of neurofilaments, disruption of the rough endoplasmic reticulum and free ribosome loss, and accumulation of large dense core vesicles and autophagic vacuoles. Accompanying these changes there was an increase in immunostaining for (a) phosphorylated neurofilaments, (b) calcitonin gene-related peptide (CGRP) and (c) the autop...Continue Reading

Associated Clinical Trials

Jul 2, 2017·Marie Catherine Boll Woehrlen

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Citations

Dec 31, 2010·Cellular and Molecular Neurobiology·Graciela L Mazzone, Andrea Nistri
Aug 12, 2010·Behavioural Pharmacology·Livia PasqualiFrancesco Fornai
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