Fullerene C60 Prevents Neurotoxicity Induced by Intrahippocampal Microinjection of Amyloid-β Peptide
Abstract:The dynamics of the state of hippocampal pyramidal neurons after intrahippocampal microinjections of (1) amyloid-β 25–35 (1.6 nmol/1 μl), (2) an aqueous molecule-colloidal solution of C60 (0.46 nmol/1 μl) and (3) an aqueous molecule-colloidal solution of C60 before amyloid-β 25–35 administration were analysed in rats. This model allowed us to study the role of amyloid-β 25–35 in the pathogenesis of Alzheimer's disease and to test anti-amyloid substances. Methods of fluorescent (acridine orange) and brightfield (cresyl violet and immunohistochemistry) microscopy were used. Acridine orange staining indicated changes in protein synthesis intensity due to alterations in the rRNA state of neuron ribosomes. One day after administration of amyloid-β 25–35, the intensity of protein synthesis in the population of morphologically intact cells decreased by 45%. By day 14, degeneration occurred in the majority of pyramidal cells, and amyloid-β 25–35 deposits were observed in the neuronal cytoplasm. In necrotic cells, acridine orange staining of the cytoplasm was drastically increased as a result of RNA degradation rather than due to an increase in protein synthesis. Because amyloid-β 25–35 administration provoked oxidative stress, we assumed that an aqueous molecule-colloidal solution of C60 administered before amyloid-β 25–35 prevented protein synthesis changes on day 1, while acting as an antioxidant, and by day 14 it inhibited neurodegeneration and amyloid-β 25–35 accumulation. Based on the data that an aqueous molecule-colloidal solution of C60 prevented amyloid-β 25–35 aggregation in in vitro experiments and based on our present evidence on the antitoxicity of an aqueous molecule-colloidal solution of C60, we suggest that functionalised C60 prevents/diminishes amyloid-β 25–35 aggregation in vivo as well. Thus, an aqueous molecule-colloidal solution of C60 administered at a low concentration before amyloid-β 25–35, prevented disturbances in protein synthesis, neurodegeneration and formation amyloid-β 25–35 deposits in hippocampal pyramidal neurons in vivo. This evidence gives promise that functionalised C60 can be used to develop anti-amyloid drugs combining antioxidant and anti-aggregative properties.
Document Type: Research Article
Publication date: January 1, 2012
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