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

International Journal of Molecular Sciences

Virginio Garcia-Lopez¹  Carlos Gutierrez-Merino¹  Jairo Salazar¹  Joana Poejo¹  Virginio Garcia-Martinez¹  Carmen Lopez-Sanchez¹ 

[1]Instituto de Biomarcadores de Patologias Moleculares, Universidad de Extremadura, 06006 Badajoz, Spain

关键词: 3-nitropropionic acid;    rat brain;    A1 astrocytes;    complement component 3;    cytokines IL-1α;    TNF-α and C1;   

DOI  :  10.3390/ijms21103609

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown