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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Neuroplasticity and Development
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1362365
This article is part of the Research Topic Editors' Showcase: Neuroplasticity and Development View all 3 articles

Exploring the role of Cdk5 on Striatal Synaptic Plasticity in a 3-NP-Induced Model of Early Huntington's disease

Provisionally accepted
Elizabeth Hernández-Echeagaray Elizabeth Hernández-Echeagaray 1*Jorge A. Miranda-Barrientos Jorge A. Miranda-Barrientos 2
  • 1 Biomedicine Research Unit, Faculty of Higher Education Iztacala, National Autonomous University of Mexico, Tlalnepantla de Baz, Mexico
  • 2 Lieber Institute for Brain Development, Baltimore, Maryland, United States

The final, formatted version of the article will be published soon.

    Impaired mitochondrial function has been associated with the onset of neurodegenerative diseases. Specifically, certain mitochondrial toxins, such as 3-nitropropionic acid (3-NP), initiate cellular changes within the striatum that closely resemble the pathology observed in Huntington's Disease (HD). Among the pivotal signaling molecules contributing to neurodegeneration, Cyclin-dependent kinase 5 (Cdk5) stands out. Notably, Cdk5 has been implicated not only in cellular pathology but also in the modulation of synaptic plasticity.Given its widespread presence in the striatum, this study seeks to elucidate the potential role of Cdk5 in the induction of corticostriatal synaptic plasticity in murine striatal cells subjected to sub-chronic doses of 3-NP in vivo, aiming to mimic the early stages of HD. Immunostaining analyses revealed an increase of Cdk5 in tissue from animals treated with 3-NP without changing protein level significantly. Regarding striatal plasticity, LTD was induced in both control and 3-NP cells when recorded in voltage clamp mode. The Cdk5 inhibitor Roscovitine reduced LTD in most cells. A minority subset of cells exhibited LTP generation in the presence of Roscovitine. The inhibitor of D1 receptors SCH23390, prevented LTP in 3/9 cells implying that MSN cells lacking D1/PKA activation were capable of LTP induction when Cdk5 was also blocked. Nevertheless, the co-administration of H89 the PKA inhibitor plus Roscovitine prevented the generation of any type of plasticity in all recorded cells. These findings show the impact of 3-NP treatment on striatal plasticity and suggest that Cdk5 in early neurodegeneration may attenuate signaling pathways that leads neurons to increase its activity.

    Keywords: Cdk5 1, Neuroprotection 2, Plasticity 3, DARPP-32 4, 3-NP 5

    Received: 28 Dec 2023; Accepted: 09 Oct 2024.

    Copyright: © 2024 Hernández-Echeagaray and Miranda-Barrientos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Elizabeth Hernández-Echeagaray, Biomedicine Research Unit, Faculty of Higher Education Iztacala, National Autonomous University of Mexico, Tlalnepantla de Baz, Mexico

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