Feng Bao¹ and Danxia Liu^1,2*

Amyotrophic Lateral Sclerosis (ALS) is a progressive motoneuron degenerative disease; its cause and mechanisms of pathogenesis remain obscure. Apoptosis may be one of the pathways responsible for motoneuron death in ALS. The present study is to further explore the role of apoptosis in ALS. Using a mutant Cu, Zn-superoxide dismutase (mSOD1) transgenic mouse model, we investigated the correlation between SOD1 mutation and neuronal and glial apoptosis in different brain regions. TUNEL-fluorescence staining and ELISA quantification found significantly more DNA fragmentation in mSOD1 mice than in controls. Double staining with TUNEL + an anti-choline acetyltransferase antibody showed many TUNEL-positive motoneurons and glial cells in the spinal cord and brain stem of mSOD1 mice, but not in the controls. Transmission electron microscopy confirmed neuronal and glial apoptosis in the spinal cord, brain stem, and motor cortex by specific morphological features of apoptosis. Double staining with TUNEL + an anti-neuron-specific enolase antibody showed many TUNEL-positive neurons in both the motor and sensory cortices of mSOD1 mice, but not in the controls. Counting the number of TUNEL-positive neurons in the sections from the three mouse groups showed significantly more TUNEL-positive neurons in both the motor and sensory cortices of mSOD1 mice than in the corresponding regions of control mice. There is no significant difference between motor and sensory cortices of mSOD1 mice. These results provide firm in vivo evidence that SOD1 mutation induced apoptosis of motoneurons and non-motoneuron cells in motoneuron-enriched brain regions. Therefore, apoptosis is not specific for motoneuron death, but a common pathway causing neuronal and glial degeneration and death in motoneuron-enriched brain regions. SOD1 mutation also induced apoptosis in sensory neurons of sensory cortex. Together, these findings imply that apoptosis might be one of pathways in which the non-neuronal cells and non-motoneuron-enriched brain regions involve in motoneuron death in ALS.
Keywords: Amyotrophic Lateral Sclerosis; Cu, Zn-Superoxide Dismutase Mutation; Neuronal And Glial Apoptosis; Motoneuron Degeneration; Transgenic Mouse Model; Transmission Electron Microscopy

Cite this Article: Bao F, Liu D. Apoptosis of Moto- and Non-Motoneurons within Moto- And Non-Motoneuron-Enriched Brain Regions in a Mutant Cu, Zn-Superoxide Dismutase Transgenic Mouse Model of Amyotrophic Lateral Sclerosis. Sci J Mult Scler. 2018; 2(1): 001-009.

Published: 19 February 2018