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Cortical Synaptic Reorganization Under Chronic Arsenic Exposure

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Abstract

There is solid epidemiological evidence that arsenic exposure leads to cognitive impairment, while experimental work supports the hypothesis that it also contributes to neurodegeneration. Energy deficit, oxidative stress, demyelination, and defective neurotransmission are demonstrated arsenic effects, but it remains unclear whether synaptic structure is also affected. Employing both a triple-transgenic Alzheimer’s disease model and Wistar rats, the cortical microstructure and synapses were analyzed under chronic arsenic exposure. Male animals were studied at 2 and 4 months of age, after exposure to 3 ppm sodium arsenite in drinking water during gestation, lactation, and postnatal development. Through nuclear magnetic resonance, diffusion-weighted images were acquired and anisotropy (integrity; FA) and apparent diffusion coefficient (dispersion degree; ADC) metrics were derived. Postsynaptic density protein and synaptophysin were analyzed by means of immunoblot and immunohistochemistry, while dendritic spine density and morphology of cortical pyramidal neurons were quantified after Golgi staining. A structural reorganization of the cortex was evidenced through high-ADC and low-FA values in the exposed group. Similar changes in synaptic protein levels in the 2 models suggest a decreased synaptic connectivity at 4 months of age. An abnormal dendritic arborization was observed at 4 months of age, after increased spine density at 2 months. These findings demonstrate alterations of cortical synaptic connectivity and microstructure associated to arsenic exposure appearing in young rodents and adults, and these subtle and non-adaptive plastic changes in dendritic spines and in synaptic markers may further progress to the degeneration observed at older ages.

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Acknowledgements

The help and facilities provided by Azucena Aguilar Vázquez and JTEJ (always and never) are gratefully acknowledged.

Funding

This research was supported by CONACYT (Fellowship 503319 for S.A.N, Grant 293 183078 for I.G.B) and DGAPA-UNAM IN203616 for S.D.-C.

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Authors and Affiliations

  1. Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico

    Sandra A. Niño, Erika Chi-Ahumada & María E. Jiménez-Capdeville

  2. División de Neurociencias, Centro de Investigación Biomédica de Occidente, IMSS. Guadalajara, Jalisco, Mexico

    Nallely Vázquez-Hernández, Fabiola L. Martín-Amaya-Barajas & Ignacio González-Burgos

  3. Facultad de Agronomía y Veterinaria, Universidad Autónoma de San Luis Potosí, Soledad de Graciano Sánchez, San Luis Potosí, Mexico

    Jaime Arevalo-Villalobos

  4. Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico

    Sofía Díaz-Cintra

  5. Laboratorio de Biomedicina, Unidad Académica Multidisciplinaria Zona Media, Universidad Autónoma de San Luis Potosí, Rio Verde, San Luis Potosí, Mexico

    Guadalupe Martel-Gallegos

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  1. Sandra A. Niño
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  2. Nallely Vázquez-Hernández
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  8. Ignacio González-Burgos
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  9. María E. Jiménez-Capdeville
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Correspondence to María E. Jiménez-Capdeville.

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Niño, S.A., Vázquez-Hernández, N., Arevalo-Villalobos, J. et al. Cortical Synaptic Reorganization Under Chronic Arsenic Exposure. Neurotox Res 39, 1970–1980 (2021). https://doi.org/10.1007/s12640-021-00409-y

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  • DOI: https://doi.org/10.1007/s12640-021-00409-y

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