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Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif
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 cytoplasmi...
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Published in: | Journal of NeuroVirology 2021 |
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creator | Ghassemi, Soheil Asgari, Tara Pourbadie, Hamid Gholami Prehaud, Christophe Lafon, Monique Naderi, Nima Gholami, Alireza Azadmanesh, Kayhan Sayyah, Mohammad |
description | 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 (~108 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 |
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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 (~108 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. 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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 (~108 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. 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title | Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif |
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