Background: Several evidence suggest HSV-1 as a potential risk factors for Alzheimer’s disease (AD). Objective: Herein we design in vitro and in vivo study to evaluate whether HSV-1 primary infection, in glia/neuron cultures, and repeated HSV-1 reactivations, in mice, may concur to accumulation of the main AD hallmarks, as b-amyloid peptides (Aβs) and neurofibrillary tangles, mainly composed by hyperphosphorylated tau. We also evaluated the potential role of HSV-1 in inducing oxidative stress and neuroinflammation, in terms of cytokines production and gliosis. Patients and Methods / Material and Methods: HSV-1 infected BALB/c mice were subjected to multiple virus reactivations. Virus replication in the brain was analyzed through PCR and RT-PCR. AD and oxidative stress hallmarks were analyzed by multiplex, immunofluorescence, western blotting and fluorymetry Results: We found that HSV-1, 4h after infection, induces in glial/neuronal cells a significant increase in the level of ROS and HNE, a marker of lipid peroxidation. This timing is consistent with our previous data showing the activation of redox-regulated pathway inducing Aβs production. Following HSV-1 multiple reactivations, we found in mouse brains: 1) viral TK and ICP4 genes in cortex and hippocampal tissues, indicating that HSV-1 is able to reach and replicate in those brain regions mostly affected during AD; 2) increased levels of HNE, protein nytrosylation (3-NT), and carbonylation; 3) enhanced levels of IL-6, IL-1b cytokines and gliosis; 4) accumulation of Aβs and altered tau phosphorylation. Conclusion: Altogether these data support the hypothesis that repeated HSV-1 infections may contribute to the neurodegeneration typical of AD and suggest a potential pathogenic role for virus-induced oxidative stress and neuroinflammation.
Herpes simplex virus type 1 (hsv-1) infection as a risk factor for ad: possible role of neuroinflammation and oxidative stress / Palamara, A. T.; Fabiani, M.; Marcocci, M. E.; Piacentini, R.; Paccagnini, D.; Pilenzi, L.; Napoletani, G.; Grassi, C.; De Chiara, G.. - In: JOURNAL OF THE NEUROLOGICAL SCIENCES. - ISSN 0022-510X. - 381:(2017), pp. 93-94. [10.1016/j.jns.2017.08.308]