The rabies glycoprotein C-terminal peptide attenuates LPS-induced synaptic dysfunction and cognitive impairment in male rats

The rabies virus exhibits a specific neurotropism for neurons within the central nervous system. It encodes five proteins, one of them is glycoprotein RVG, which integrates into the host cell's plasma membrane. Our previous research found that RVG expression in hippocampal cells enhances memory and potentiates synaptic plasticity, dependent on its PDZ-binding motif (PBM). In this study, we aim to express a peptide from the carboxyl end of RVG, named Neurovita 2 (NV2), in the hippocampus, to investigate its effects on learning, memory, and synaptic plasticity. 2 μl of a lentiviral vector (10 8 T.U. /ml) carrying the NV2 or ΔNV2 (lacking the four C-terminal amino acids) genome was microinjected into the dorsal hippocampus of male Wistar rats. In a subsequent experiment, one week after the lentiviral vector treatment, we microinjected lipopolysaccharide (LPS) 30 min pre-training into the dorsal hippocampus. Spatial and inhibitory memory tests were done using the Morris water maze and shuttle box test, respectively. The presence of NV2/ΔNV2-expressing neuronal cells was confirmed through fluorescent microscopy after the rats were euthanized. Results showed that LPS impaired spatial learning and memory. However, NV2, but not ΔNV2, ameliorated the spatial learning and memory deficits in LPS-treated rats. Moreover, NV2 expression in the hippocampus mitigated LPS-induced deficits in both short- and long-term synaptic plasticity. Our findings suggest that NV2 expression in the hippocampus can enhance synaptic function and improve memory performance in a neuroinflammation rat model, warranting further studies on its effects in preclinical neurodegenerative conditions.