The Neurogenesis Actuator and NR2B/NMDA Receptor Antagonist Ro25-6981 Consistently Improves Spatial Memory Retraining Via Brain Region-Specific Gene Expression
| Autor: | Marina A. Gruden, Robert David Edmund Sewell, Olga Solovieva, Zinaida I. Storozheva, Vladimir V. Sherstnev, Alexander M. Ratmirov |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Neurogenesis Hippocampus Morris water navigation task Cell Cycle Proteins Water maze Hippocampal formation Biology Receptors N-Methyl-D-Aspartate Spatial memory Article S100 Calcium Binding Protein A6 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Phenols Piperidines Basic Helix-Loop-Helix Transcription Factors Animals Rats Wistar Prefrontal cortex Ro25-6981 Caspase 3 Brain General Medicine NR2B/NMDA glutamate receptors Rats 030104 developmental biology nervous system NMDA receptor Gene expression Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Molecular Neuroscience |
| ISSN: | 1559-1166 0895-8696 |
| DOI: | 10.1007/s12031-018-1083-5 |
| Popis: | NR2B-containing NMDA (NR2B/NMDA) receptors are important in controlling neurogenesis and are involved in generating spatial memory. Ro25-6981 is a selective antagonist at these receptors and actuates neurogenesis and spatial memory. Inter-structural neuroanatomical profiles of gene expression regulating adult neurogenesis and neuroapoptosis require examination in the context of memory retrieval and reversal learning. The aim was to investigate spatial memory retrieval and reversal learning in relation to gene expression-linked neurogenetic processes following blockade of NR2B/NMDA receptors by Ro25-6981. Rats were trained in Morris water maze (MWM) platform location for 5 days. Ro25-6981 was administered (protocol days 6–7) followed by retraining (days 15–18 or 29–32). Platform location was tested (on days 19 or 33) then post-mortem brain tissue sampling (on days 20 or 34). The expression of three genes known to regulate cell proliferation (S100a6), differentiation (Ascl1), and apoptosis (Casp-3) were concomitantly evaluated in the hippocampus, prefrontal cortex, and cerebellum in relation to the MWM performance protocol. Following initial training, Ro25-6981 enhanced visuospatial memory retrieval performance during further retraining (protocol days 29–32) but did not influence visuospatial reversal learning (day 33). Hippocampal Ascl1 and Casp-3 expressions were correspondingly increased and decreased while cerebellar S100a6 and Casp-3 activities were decreased and increased respectively 27 days after Ro25-6981 treatment. Chronological analysis indicated a possible involvement of new mature neurons in the reconfiguration of memory processes. This was attended by behavioral/gene correlations which revealed direct links between spatial memory retrieval enhancement and modified gene activity induced by NR2B/NMDA receptor blockade and upregulation. |
| Databáze: | OpenAIRE |
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