Abstract
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.
Highlights
Recent evidence has implicated N-methyl-d-aspartate receptors (NMDARs) in several aspects of learning ability and behavioral flexibility in rodents (Delgado-García and Gruart 2017; Zhou and Wollmuth 2017)
There are no data concerning NR2B/NMDA receptor antagonism on gene expression implicated in neurogenesis and neuroapoptosis in different brain structures either in naïve animals or during consolidation and reconsolidation of spatial performance
Throughout the whole protocol, there were no differences between the platform location times expressed in animals after Ro25-6981 administration compared with saline controls and this absence of difference persisted even in the platform relocation test [F(2.21) = 0.5, P > 0.1]
Summary
Recent evidence has implicated N-methyl-d-aspartate receptors (NMDARs) in several aspects of learning ability and. The expression of three genes known to regulate cell proliferation (S100a6), differentiation (Ascl1), and apoptosis (Casp-3) have been concomitantly evaluated in the rat hippocampus, prefrontal cortex, and cerebellum with respect to water maze spatial memory performance. There are no data concerning NR2B/NMDA receptor antagonism on gene expression implicated in neurogenesis and neuroapoptosis in different brain structures either in naïve animals or during consolidation and reconsolidation of spatial performance. The aim was to study spatial memory retrieval, reversal learning, and gene expression following blockade of NR2B/NMDA receptors by the neurogenesis actuator Ro25-6981 as a potential memory enhancer. Regarding this point, hippocampal, prefrontal cortical and cerebellar brain areas were selected for study. This was because it has been previously shown that there are integrative relationships between Casp, Ascl, and S100a6 genes in all three of these neuroanatomical structures with respect to spatial memory (Gruden et al 2013)
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