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Gold Nanoparticles Treatment Reverses Brain Damage in Alzheimer’s Disease Model

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Abstract

Alzheimer’s disease (AD) is characterized by amyloid (A)β peptide accumulation and intracellular neurofibrillary tangles. New hypotheses have suggested that AD involves neuroinflammation and oxidative stress. Gold nanoparticles (AuNP) presents anti-inflammatory and antioxidant characteristics. The present study evaluated the AuNP treatment on an AD model (okadaic acid, OA). Male Wistar rats were injected intracerebroventricularly with OA (100 μg); 24 h later they were treated with 20-nm AuNP (at a dose 2.5 mg/kg) every 48 h for 21 days. The following groups were separated (n = 12/group): Sham, AuNP, OA, and OA + AuNP. OA increases Tau phosphorylation in the cortex and hippocampus, while AuNP treatment maintained it as normal. Spatial memory was impaired by OA, and AuNP treatment prevented this deficit. Neurotrophic factors (BDNF and NGF- β) in the cortex and hippocampus were decreased by OA. The OA and OA + AuNP groups showed increased interleukin (IL)-1 β in the hippocampus and cortex, and the AuNP group showed increased IL-1 β in the hippocampus. In both groups, S100 levels in the cortex and hippocampus were increased by OA. IL-4 was increased in OA + AuNP animals. AuNPs prevented oxidative stress (sulfhydryl and nitrite levels) in brain structures induced by OA. Moreover, OA modulated ATP synthase activity, and AuNP maintained normal brain mitochondrial function. The antioxidant capacities were reduced by OA, and AuNP restored antioxidant status (SOD, catalase activities and GSH levels) on brain. OA-induced damage on brain tissues, and long-term AuNP treatment prevented the neuroinflammation, modulation of mitochondrial function, and impaired cognition induced by AD model, showing that AuNPs may be a promising treatment for neurodisease caused by these elements.

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Funding

This work was supported by FAPESC-PPSUS 2016, CNPq, Instituto Nacional de Neurociência Translacional-INNT #465346/2014-6, and Unesc.

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  1. Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Bairro Universitário, Criciúma, SC, 88806-000, Brazil

    Natalia dos Santos Tramontin, Sabrina da Silva, Kellen Simon Ugioni, Paula Bortuluzzi Canteiro, Gustavo de Bem Silveira, Carolini Mendes, Paulo Cesar Lock Silveira & Alexandre Pastoris Muller

  2. Universidade de Rio Verde, Rio Verde, GO, 75901-970, Brazil

    Rychard Arruda

  3. Programa de Pos Graduação em Farmacologia, UFSC, Florianópolis, SC, Brazil

    Alexandre Pastoris Muller

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dos Santos Tramontin, N., da Silva, S., Arruda, R. et al. Gold Nanoparticles Treatment Reverses Brain Damage in Alzheimer’s Disease Model. Mol Neurobiol 57, 926–936 (2020). https://doi.org/10.1007/s12035-019-01780-w

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