IJAE

Neuroinflammation is a protective mechanism with the aim to clear infective agents and also to repair, regenerate and remove the damaged cells [1]. The chronic inflammation and the resulting prolonged activation of brain cells, however, drive to alterations in neuronal structure and functions leading to neurodegeneration [2]. Upon injury, the astrocytes have the potential to acquire neural stem cell properties to be reprogrammed into neurons [3], but the chronic exposure to inflammatory signals diminishes progressively the neuron’s recovery due to the inhibitory environment and the glial scar formation [4]. In this work we investigated the eff ects of lactoferrin, an iron-binding glycoprotein with known immunomodulatory functions, on the eprogramming properties of DI-TNC1 astrocyte cell line. To mimic a chronic inflammatory environment, the astrocytes culture was treated with lactoferrin (LF) (4μg/ml), or LPS (0,4μg/ml), or LF+LPS, adding LPS 24 hours later the LF treatment. Then, cells were analyzed at three time points (t), respectively, at 2, 9 and 16 days from the fi rst stimulation. We showed that LF boosts the neurogenic properties of the astrocytes at t2 and t9 evidenced by the overexpression of the stem cell markers, SOX-2 and Oct4, and the neural diff erentiation marker, β-tubulin III. In addition, we also performed a morphological analysis, evidencing that the number of cells with neuronal-like morphology and the length of neurites were increased by the pre-treatment with LF. Interestingly, aft er 16 days, the LPS treated-cells showed signs of necrosis, whereas the LF+LPS-treated cells exhibited neural morphological features without signs of suff ering. Taken together, these results demonstrate the lactoferrin capability to trigger and boost the astrocytes reprogramming into cells with neural phenotype, suggesting its possible protective effects in a context of chronic infl ammation.