Gene transfer of NMDAR1 subunit sequences to the rat CNS using herpes simplex virus vectors interfered with habituation
VT Cheli, MF Adrover, C Blanco, ER Verde… - Cellular and molecular …, 2002 - Springer
VT Cheli, MF Adrover, C Blanco, ER Verde, V Guyot-Revol, R Vidal, E Martin, L Alche…
Cellular and molecular neurobiology, 2002•SpringerThe aim is to study some roles of the hippocampal NMDA receptor, by modifying the
expression of the essential NRl subunit, with temporal and spatial restrictions in the central
nervous system (CNS) of the rat. 2. Due to their neurotropism and the size of inserts they can
accomodate, herpes simplex virus type-l (HSV-1) derived amplicon vectors were used to
transfer sequences, either in sense (+) or antisense (-) orientations, of the NRl subunit gene,
or of the green fluorescent protein (GFP) gene, into the CNS. 3. Vector expression in cell …
expression of the essential NRl subunit, with temporal and spatial restrictions in the central
nervous system (CNS) of the rat. 2. Due to their neurotropism and the size of inserts they can
accomodate, herpes simplex virus type-l (HSV-1) derived amplicon vectors were used to
transfer sequences, either in sense (+) or antisense (-) orientations, of the NRl subunit gene,
or of the green fluorescent protein (GFP) gene, into the CNS. 3. Vector expression in cell …
Abstract
1. The aim is to study some roles of the hippocampal NMDA receptor, by modifying the expression of the essential NRl subunit, with temporal and spatial restrictions in the central nervous system (CNS) of the rat.
2. Due to their neurotropism and the size of inserts they can accomodate, herpes simplex virus type-l (HSV-1) derived amplicon vectors were used to transfer sequences, either in sense (+) or antisense (-) orientations, of the NRl subunit gene, or of the green fluorescent protein (GFP) gene, into the CNS.
3. Vector expression in cell lines was followed by GFP autofluorescence, immunofluorescence and western blot.
4. The vectors were inoculated into the dorsal hippocampus of adult male Wistar rats, which were evaluated for habituation to an open field, and then, for expression of the transgenes, by autofluorescence and western blot; the expression mainly happened in pyramidal cells of CA1.
5. The animals injected with vectors carrying the NRl(+) transgene showed habituation to the new environment, as also happened with rats injected with vectors carrying only the GFP transgene.
6. In contrast, animals injected with vectors carrying NRl(-) sequence, did not show habituation. This might be retrograde amnesia or disability to record the trace, suggesting that the NRl subunit in the dorsal hippocampus, is involved in habituation to a new environment.
7. HSV-1 derived amplicon vectors appear to be useful tools to modify endogenous gene expression, at a defined period, in restricted regions of the CNS.
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