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Open AccessArticle

Early Reactive A1 Astrocytes Induction by the Neurotoxin 3-Nitropropionic Acid in Rat Brain

1
Instituto de Biomarcadores de Patologias Moleculares, Universidad de Extremadura, 06006 Badajoz, Spain
2
Departamento de Anatomia y Embriologia Humana, Facultad de Medicina, Universidad de Extremadura, 06006 Badajoz, Spain
3
Departamento de Enfermeria, Facultad de Medicina, Universidad de Extremadura, 06006 Badajoz, Spain
4
Departamento de Quimica, Universidad Nacional Autonoma de Nicaragua-Leon, Leon 21000, Nicaragua
5
Departamento de Bioquimica y Biología Molecular y Genetica, Facultad de Ciencias, Universidad de Extremadura, 06006 Badajoz, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3609; https://doi.org/10.3390/ijms21103609
Received: 7 April 2020 / Revised: 17 May 2020 / Accepted: 18 May 2020 / Published: 20 May 2020
3-Nitropropionic acid (NPA) administration to rodents produces degeneration of the striatum, accompanied by neurological disturbances that mimic Huntington’s disease (HD) motor neurological dysfunctions. It has been shown that inflammation mediates NPA-induced brain degeneration, and activated microglia secreting cytokines interleukin-1α (IL-1α) and tumor necrosis factor α (TNFα) can induce a specific type of reactive neurotoxic astrocytes, named A1, which have been detected in post-mortem brain samples of Huntington’s, Alzheimer’s, and Parkinson’s diseases. In this work we used an experimental model based on the intraperitoneal (i.p.) administration of NPA to adult Wistar rats at doses that can elicit extensive brain degeneration, and brain samples were taken before and after extensive brain damage monitored using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Western blots and immunohistochemistry of brain slices show that i.p. NPA injections elicit significant increase in the expression levels of C3α subunit, a marker of generation of neurotoxic A1 astrocytes, and of cytokines IL-1α, TNFα, and C1q within the striatum, hippocampus, and cerebellum before the appearance of the HD-related neurological dysfunctions and neuronal death induced by NPA. Noteworthy, NPA administration primarily induces the generation of A1 astrocytes in the more recent phylogenetic area of the rat cerebellum. We conclude that the activation of complement C3 protein in the brain from Wistar rats is an early event in NPA-induced brain neurodegeneration. View Full-Text
Keywords: 3-nitropropionic acid; rat brain; A1 astrocytes; complement component 3; cytokines IL-1α; TNF-α and C1 3-nitropropionic acid; rat brain; A1 astrocytes; complement component 3; cytokines IL-1α; TNF-α and C1
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Lopez-Sanchez, C.; Garcia-Martinez, V.; Poejo, J.; Garcia-Lopez, V.; Salazar, J.; Gutierrez-Merino, C. Early Reactive A1 Astrocytes Induction by the Neurotoxin 3-Nitropropionic Acid in Rat Brain. Int. J. Mol. Sci. 2020, 21, 3609.

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