Early Administration of Methylene Blue Attenuates Mitochondrial Dysfunction and Cognitive Deficits in a Model of Huntington’s Disease
5 affiliations
- 1Laboratorio de Psicobiología, Departamento de Ciencias de la Tierra y de la Vida, Centro Universitario de los Lagos, , Lagos de Moreno 47000, Jalisco, Mexico;
- 2Laboratorio de Neurofisiología del Músculo Esquelético, Centro Universitario de Investigaciones Biomédicas, , Colima 28040, Colima, Mexico;
- 3Laboratorio de Neuroplasticidad, Centro de Investigación Biomédica de Michoacán, , Morelia 58341, Michoacán, Mexico;
- 4Laboratorio de Bioquímica, Instituto de Investigaciones Químico-Biológicas, , Morelia 58030, Michoacán, Mexico;
- 5Laboratorio de Neurofisiología Clínica y Experimental, Centro de Investigación Biomédica de Michoacán, , Morelia 58341, Michoacán, Mexico
Abstract
Huntington’s disease (HD) is a fatal neurodegenerative disorder marked by progressive motor, cognitive, and psychiatric impairments, for which no disease-modifying therapies exist. Mitochondrial dysfunction is an early feature of HD, highlighting the need to target bioenergetic deficits early. We evaluated the neuroprotective effects of methylene blue (MB) in a 3-nitropropionic acid (3-NP)-induced HD-like rat model characterized by mitochondrial dysfunction and striatal injury. Male Wistar rats received MB for 14 days during 3-NP administration. Behavioral performance was assessed, followed by biochemical and histological analyses of the striatum. MB improved cognitive performance and partially improved specific aspects of motor coordination. At the mitochondrial level, MB restored Complex II activity, membrane potential index, reduced reactive oxygen species (ROS), and modulated mitochondrial function, but did not rescue Complex I. Histologically, MB attenuated striatal histopathological damage. These results suggest that methylene blue has neuroprotective effects in the early stages, particularly at the mitochondrial and cognitive levels. Its limited impact on other behaviors and systemic parameters could indicate that its efficacy depends on timing or duration. Overall, this study supports early mitochondrial targeting in HD therapy and shows methylene blue as a promising, though partial, disease-modifying candidate.
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BibTeX
@article{huertacervantes2026early,
title = {{Early Administration of Methylene Blue Attenuates Mitochondrial Dysfunction and Cognitive Deficits in a Model of Huntington’s Disease}},
author = {Maribel Huerta-Cervantes and Donovan J. Peña-Montes and Miguel Ángel López-Vázquez and Alfredo Saavedra-Molina and María Isabel Pérez-Vega and María Esther Olvera-Cortés},
journal = {Biology},
year = {2026},
month = oct,
doi = {10.3390/biology15201801},
url = {https://europepmc.org/article/PMC/PMC13701637},
note = {CC BY},
}
RIS
TY - JOUR
TI - Early Administration of Methylene Blue Attenuates Mitochondrial Dysfunction and Cognitive Deficits in a Model of Huntington’s Disease
AU - Maribel Huerta-Cervantes
AU - Donovan J. Peña-Montes
AU - Miguel Ángel López-Vázquez
AU - Alfredo Saavedra-Molina
AU - María Isabel Pérez-Vega
AU - María Esther Olvera-Cortés
PY - 2026
DA - 2026/10/01
JO - Biology
DO - 10.3390/biology15201801
UR - https://europepmc.org/article/PMC/PMC13701637
AB - Huntington’s disease (HD) is a fatal neurodegenerative disorder marked by progressive motor, cognitive, and psychiatric impairments, for which no disease-modifying therapies exist. Mitochondrial dysfunction is an early feature of HD, highlighting the need to target bioenergetic deficits early. We evaluated the neuroprotective effects of methylene blue (MB) in a 3-nitropropionic acid (3-NP)-induced HD-like rat model characterized by mitochondrial dysfunction and striatal injury. Male Wistar rats received MB for 14 days during 3-NP administration. Behavioral performance was assessed, followed by biochemical and histological analyses of the striatum. MB improved cognitive performance and partially improved specific aspects of motor coordination. At the mitochondrial level, MB restored Complex II activity, membrane potential index, reduced reactive oxygen species (ROS), and modulated mitochondrial function, but did not rescue Complex I. Histologically, MB attenuated striatal histopathological damage. These results suggest that methylene blue has neuroprotective effects in the early stages, particularly at the mitochondrial and cognitive levels. Its limited impact on other behaviors and systemic parameters could indicate that its efficacy depends on timing or duration. Overall, this study supports early mitochondrial targeting in HD therapy and shows methylene blue as a promising, though partial, disease-modifying candidate.
SN - 2079-7737
ER -