Metabolic changes induced by interferon-\u3b1 exposure in an in vitro model of human neurons

The human neuroblastoma SH-SY5Y cell line is a third successive subclone of the SK-N-SH line, originally established from a bone marrow biopsy of a neuroblastoma patient. These cells possess many characteristics of neurons, and they represent one of the most-used models for studying cellular events and mechanisms involved in neurotoxicity and neurodegeneration or even in neuroprotection. We have been using these cells as a tools to evaluate the largely unexplored effects induced by interferon (IFN)- alpha (a clinically used type I IFN) exposure on neurons. Interferons are cytokines endowed with a pleiotropic spectrum of biological properties, including immunomodulation, antiviral and pro-inflammatory activity. Beside the periphery, and cells of the immune system, type I IFNs may have broad-ranging actions also in the brain, affecting neuronal differentiation, survival and synaptic plasticity. We recently demonstrated that exposure to IFN-\u3b1 induces neurotoxic effects in a time e dose dependent manner in SH-SY5Y cells by impairing mitochondrial integrity and activity, recruitment of Bcl-2 family members, induction of oxidative stress (increases reactive oxygen species). Indeed following 72 hours exposure to this cytokine we found increased early apoptosis (Alboni et al., 2013). This prompted us to investigate the changes in the metabolic profile of live SH-SY5Y cells exposed to IFN-\u3b1 (72 h) using 1H High Resolution-Magic Angle Spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy. Firstly, this technique enabled us to characterize the metabolic signature of intact SH-SY5Y cells. Several metabolites, including amino acids, osmolites, phospholipids, organic acids, sugars and polyols have been identified. Moreover, we found that human neuronal cells exposed to IFN-\u3b1 for 72 h had significantly increased concentration of lactate (\uf044% 93.9), taurine (\uf044% 117.7), myo-inositol (\uf044% 123.2), scyllo-inositol (\uf044% 117.4), glycerolphosphocholine (\uf044% 135.2) and creatine (\uf044% 159.9) compared with the vehicle-treated control cells. These data provide the demonstration that IFN-\u3b1 exposure induces metabolic changes in human neuron-like cells. Moreover, these results may contribute to explain IFN-\u3b1-induced central side-effects often observed following IFN-\u3b1 treatment for viral infection and malignancies