Bruno Bandiera (Italy)
Università Cattolica del Sacro Cuore NeuroscienceAuthor Of 1 Presentation
RECURRENT HERPES SIMPLEX VIRUS TYPE-1 REACTIVATIONS IN ADULT MICE BRAIN ALTER SYNAPTIC FUNCTIONS AND MEMORY: A POSSIBLE ROLE FOR IL-1Β
- Domenica D. Li Puma (Italy)
Abstract
Background and Aims:
Several evidence suggests that Herpes Simplex virus type-1 (HSV-1) infection is a risk factor for Alzheimer’s disease (AD). We recently developed a mouse model of multiple HSV-1 reactivations within the brain exhibiting accumulation of AD hallmarks and impaired hippocampal neurogenesis. Here, we investigated the impact of infection on synaptic function and memory and looked for a possible involvement of neuroinflammation.
Methods:
C57/Bl6 mice were inoculated with HSV-1 via snout abrasion and after two reactivations and treatment with IL-1R antagonist, were studied with different experimental approaches.
Results:
HSV-1-infected mice exhibited memory impairment, assessed by novel object recognition and fear conditioning tests. Specifically, in the former the preference index was 57.1±2.1% (n=15) vs 65.8±2.1% (n=16) in HSV-1- and mock-infected mice, respectively (p<0.05). The contextual fear memory was also reduced: the percentage of time spent freezing was 30.5±3.0% in HSV-1-infected mice (n=14) and 41.9±3.1% in controls (n=15; p<0.05). Long-term potentiation at the hippocampal CA3-CA1 synapses was significantly reduced in brain slices from HSV-1-infected mice compared to mock-infected ones: fEPSP amplitude was 58.2±7.9% of the baseline (n=16) vs 97.6±10.8% (n=16), p<0.05, respectively. Accordingly, we found downregulated expression of pre- and postsynaptic proteins in hippocampi of infected mice (-50% vs. mock) along with decreased dendritic spines density in CA1 neurons (-11±2%; p<0.05). These synaptic defects were associated with increased levels of the proinflammatory cytokine IL-1β (20.9±1.1 vs. 5.8±2.1 pg/mg in controls, p<0.05) and rescued by blocking IL1R.
Conclusions:
Our results suggest that HSV-1 reactivations into the brain of C57/bl6 mice induce synaptic dysfunction and cognitive decline via IL-1β.