Lactoferrin Protects against Methamphetamine Toxicity by Modulating Autophagy and Mitochondrial Status

Nutrients

Maico Polzella¹  Larisa Ryskalin²  Michela Ferrucci²  Francesco Fornai²  Paola Lenzi²  Alessandro Frati³  Carla L. Busceti³  Francesca Biagioni³ 

[1] Aliveda Laboratories, Viale Karol Wojtyla, 19, 56042 Crespina Lorenzana, Italy;Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy;Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via Atinense 18, 86077 Pozzilli, Italy;

关键词: autophagy;    lactoferrin;    methamphetamine;    cell death;    light microscopy;   

DOI  :  10.3390/nu13103356

来源: DOAJ

【 摘 要 】

Lactoferrin (LF) was used at first as a vehicle to deliver non-soluble active compounds to the body, including the central nervous system (CNS). Nonetheless, it soon became evident that, apart from acting as a vehicle, LF itself owns active effects in the CNS. In the present study, the effects of LF are assessed both in baseline conditions, as well as to counteract methamphetamine (METH)-induced neurodegeneration by assessing cell viability, cell phenotype, mitochondrial status, and specific autophagy steps. In detail, cell integrity in baseline conditions and following METH administration was carried out by using H&E staining, Trypan blue, Fluoro Jade B, and WST-1. Western blot and immuno-fluorescence were used to assess the expression of the neurofilament marker βIII-tubulin. Mitochondria were stained using Mito Tracker Red and Green and were further detailed and quantified by using transmission electron microscopy. Autophagy markers were analyzed through immuno-fluorescence and electron microscopy. LF counteracts METH-induced degeneration. In detail, LF significantly attenuates the amount of cell loss and mitochondrial alterations produced by METH; and mitigates the dissipation of autophagy-related proteins from the autophagy compartment, which is massively induced by METH. These findings indicate a protective role of LF in the molecular mechanisms of neurodegeneration.

【 授权许可】

Unknown