• Uri Nimrod Ramirez-Jarquin, Violeta Gisselle Lopez-Huerta, and Ricardo Tapia.
• Dept. of Pharmacology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Belisario Domínguez Secc 16, Tlalpan, 14080 México City, Mexico; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510-Ciudad de México, Mexico. Electronic address: uri.ramirezjarquin@cardiologia.org.mx.
• Neuroscience. 2023 Jun 15; 521: 314331-43.

AbstractMitochondrial damage is a central mechanism involved in neurological disorders as Alzheimer's, and Parkinson's diseases and amyotrophic lateral sclerosis. Energy production is the most studied mitochondrial function; however, mitochondria are also involved in processes like calcium buffering homeostasis, and cell death control during apoptosis and necrosis. Using transmission electron microscopy, in this in vivo study in male rats, we describe ultrastructural mitochondrial alterations of spinal motor neurons along chronic AMPA-induced excitotoxicity, which has been described as one of the most relevant mechanisms in ALS disease. Mitochondrial alterations begin with a crest swelling, which progresses to a full mitochondrial swelling and crest disruption. Changes on the mitochondrial morphology from elongated to a circular shape also occur along the AMPA-excitotoxicity process. In addition, by combining the TUNEL assay and immunohistochemistry for mitochondrial enzymes, we show evidence of mitochondrial DNA damage. Evidence of mitochondrial alterations during an AMPA-excitotoxic event is relevant because resembles the mitochondrial alterations previously reported in ALS patients and in transgenic familial ALS models, suggesting that a chronic excitotoxic model can be related to sporadic ALS (as has been shown in recent papers), which represent more than the 90% of the ALS cases. Understanding the mechanisms involved in motor neuron degenerative process, such as the ultrastructural mitochondrial changes permits to design strategies for MN-degeneration treatments in ALS.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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