Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif

Abstract

Rabies is a life-threatening viral infection of the brain. Rabies virus (RABV) merely infects excitable cells including neurons provoking drastic behaviors including negative emotional memories. RABV glycoprotein (RVG) plays a critical role in RABV pathogenesis. RVG interacts with various cytoplasmic PDZ (PSD-95/Dlg/ZO-1) containing proteins through its PDZ binding motif (PBM). PTZ domains have crucial role in formation and function of signal transduction.Hippocampus is one of the cerebral regions that contains high load of viral antigens. We examined impact of RVG expression in the dorsal hippocampus on aversive as well as spatial learning and memory performance in rats.Two μl of the lentiviral vector (~10 8 T.U. /ml) encoding RVG or ∆RVG (deleted PBM) genomes was microinjected into the hippocampal CA1. After one week, rat's brain was cross-sectioned and RVG/∆RVG-expressing neuronal cells were confirmed by fluorescent microscopy. Passive avoidance and spatial learning and memory were assessed in rats by Shuttle box and Morris water maze (MWM).In the shuttle box, both RVG and ∆RVG decreased the time spent in the dark compartment compared to control (p<0.05). In MWM, RVG and ∆RVG did not affect the acquisition of spatial task. RVG-expressing rats reached the platform position in the probe test sooner than control and ∆RVG groups (p<0.05). Rats expressing ∆RVG significantly swam farther from the hidden platform than RVG group (p<0.05).Our data indicate RVG expression in the hippocampus strengthens aversive and spatial learning and memory performance. The boosting effect on spatial but not avoidance memory is mediated through PBM.

Selective neurodegeneration generated by intravenous α‐synuclein pre‐formed fibril administration is not associated with endogenous α‐synuclein levels in the rat brain

“…We studied changes in behavioural performance in different functional domains of non‐transgenic, Sprague–Dawley rats up to 18‐months after a single, intravenous administration of RVG9R:PFF, PFF alone, or PBS control. We did not include animals receiving RVG9R alone, as we (and others) have previously shown that the RVG peptide when administered on its own does not generate any CNS pathology [ 10 , 18 , 19 ]. There was a significant deterioration in forelimb control in the RVG9R:PFF rats over time ( p = 0.049, Figure S2A ), although gross motor coordination and spontaneous forelimb use was not affected (Figure S2B–D ).…”

Latent toxoplasmosis impairs learning and memory yet strengthens short-term and long-term hippocampal synaptic plasticity at perforant pathway-dentate gyrus, and Schaffer collatterals-CA1 synapses

“…The avoidance learning and memory was assessed by shuttle-box apparatus according to the method that is published before 29 . After habituating the animal with chamber, it was placed in the bright chamber with the guillotine door open.…”