Acute stress-induced impairment of spatial memory is associated with decreased expression of neural cell adhesion molecule in the hippocampus and prefrontal cortex

Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Biological Psychiatry (Impact Factor: 10.26). 05/2005; 57(8):856-64. DOI: 10.1016/j.biopsych.2004.12.034
Source: PubMed


There is an extensive literature describing how stress disturbs cognitive processing and can exacerbate psychiatric disorders. There is, however, an insufficient understanding of the molecular mechanisms involved in stress effects on brain and behavior.
Rats were given spatial memory training in a hippocampus-dependent water maze task. We investigated how a fear-provoking experience (predator exposure) would affect their spatial memory and neural cell adhesion molecule (NCAM) levels in the hippocampus, prefrontal cortex (PFC), amygdala, and cerebellum.
Whereas the control (nonstress) group exhibited excellent memory for the hidden platform location in the water maze, the cat-exposed (stress) group exhibited a profound impairment of memory and a marked suppression of levels of the NCAM-180 isoform in the hippocampus. Predator stress produced a more global reduction of NCAM levels in the PFC but had no effect on NCAM levels in the amygdala and cerebellum.
This work provides a novel perspective into dynamic and structure-specific changes in the molecular events involved in learning, memory, and stress. The selective suppression of NCAM-180 in the hippocampus and the more general suppression of NCAM in the PFC provide insight into the mechanisms underlying the great sensitivity of these two structures to be disturbed by stress.

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    • " Mohapel et al . , 2013 ) . There is a substantial coincidence between this view and the data showing that conditions that reduced proliferation ( i . e . , CVS ) also affected acquisition in our MWM assessment . There is a plethora of experiments showing that intense stress impairs both neurogenesis and spatial learning ( Lemaire et al . , 2000 ; Sandi et al . , 2005 ; Yan et al . , 2011 ; Naninck et al . , 2015 ) . It seems clear that intense and / or chronic conditions impair these parameters at all stages of life and that such effects are reversible , as shown in our experiments . There are only a few experiments addressing conditions where stress stimulates proliferation and cognition . Previous"
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    ABSTRACT: In this study, we exposed adult rats to chronic variable stress (CVS) and tested the hypothesis that previous early-life exposure to stress changes the manner in which older subjects respond to aversive conditions. To this end, we analyzed the cytogenic changes in the hippocampus and hippocampal-dependent spatial learning performance. The experiments were performed on 18-month-old male rats divided into four groups as follows: Control (old rats under standard laboratory conditions), Early-life stress (ELS; old rats who were exposed to environmental noise from postnatal days, PNDs 21-35), CVS + ELS (old rats exposed to a chronic stress protocol who were previously exposed to the early-life noise stress) and CVS (old rats who were exposed only to the chronic stress protocol). The Morris Water Maze (MWM) was employed to evaluate the spatial learning abilities of the rats at the end of the experiment. Immunohistochemistry against 5'Bromodeoxyuridine (BrdU) and glial fibrillar acidic protein (GFAP) was also conducted in the DG, CA1, CA2 and CA3 regions of the hippocampus. We confocally analyzed the cytogenic (BrdU-labeled cells) and astrogenic (BrdU + GFAP-labeled cells) changes produced by these conditions. Using this procedure, we found that stress diminished the total number of BrdU+ cells over the main proliferative area of the hippocampus (i.e., the dentate gyrus, DG) but increased the astrocyte phenotypes (GFAP + BrdU). The depleted BrdU+ cells were restored when the senile rats also experienced stress at the early stages of life. The MWM assessment demonstrated that stress also impairs the ability of the rats to learn the task. This impairment was not present when the stressful experience was preceded by the early-life exposure. Thus, our results support the idea that previous exposure to mild stressing agents may have beneficial effects on aged subjects.
    Full-text · Article · Sep 2015 · Frontiers in Aging Neuroscience
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    • "Afferent nerves from cold receptors, located in the skin, terminate in the hypothalamus and then multisynaptic pathways reach limbic areas, especially the hippocampus, leading to noradrenaline release (Rintamaki, 2005; Kvetnansky et al., 2009). Considerable evidence supports a close interaction between stress and the noradrenergic system in the hippocampus (Nisenbaum et al., 1991; Britton et al., 1992; Sandi et al., 2005). "
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    ABSTRACT: Aim: Behavioral and mental changes may occur in people exposed to cold stress by decreasing their work efficiency and their mental capacity while increasing the number of accidents on the job site. The goal of this study was to explore the effect of cold stress in spatial learning performance excitability and LTP. Materials and methods: Three to four month old rats were randomly divided into four groups to form a control group and a cold stress group for each sex. The groups of cold stressed animals were placed in a cold room ambient temperature of 4°C for 2 h day. Adrenal glands and body weight (g) were recorded in control and stressed rats during the cold exposure. Spatial learning (acquisition phase) and memory (probe trial) were tested in the Morris water maze (MWM) immediately after daily exposure. Latency to locate the hidden platform, distance moved (DM), mean distance to platform, swim speed (SS) and time spent in the platform quadrant were compared between genders and treatments. Field potential recordings were made, under urethane anesthesia, from the dentate gyrus (DG) granule-cell layer, with stimulation of the medial perforant pathway 2 h after the probe trial. This study examined spatial memory as measured by MWM performance and hippocampal long-term potentiation (LTP) in the DG after exposure to cold in a repeated stress condition for 2 h/day for 5 days. Results: The cold-exposed female rats needed less time to find the hidden platform on day 1 (43.0 ± 13.9 s vs. 63.2 ± 13.2 s), day 2 (18.2 ± 8.4 s vs. 40.9 ± 12.2 s) and on day 4 (8.0 ± 2.1 s vs. 17.2 ± 7.0 s) while cold-exposed male rats showed a decreased escape latency (EL) on day 1 only (37.3 ± 12.5 s vs. 75.4 ± 13.1 s). Cold-exposed male rats spent less time in the target quadrant (30.08 ± 6.11%) than the control male rats (37.33 ± 8.89%). Two hour cold exposure decreased population spike (PS) potentiation during both induction (218.3 ± 21.6 vs. 304.5 ± 18.8%) and maintenance intervals (193.9 ± 24.5 vs. 276.6 ± 25.4%) in male rats. Meanwhile cold exposure did not affect the body weight (C: 221 ± 2.5 vs. S: 222 ± 1.7) but it impacts the adrenal gland relative weight (S: 27.1 ± 1.8 mg vs. C: 26.2 ± 1.4 mg). Conclusion: Overall, the results show that repeated cold exposure can selectively improve spatial learning in adult female rats, but impaired retention memory for platform location in male rats. It is possible that impaired LTP underlies some of the impaired retention memory caused by cold exposure in the male rats.
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    • "Thus, glucocorticoid (GR) and mineralocorticoid receptors (MR), which exhibit a different affinity for corticosterone, are heavily expressed in the hippocampus, the amygdala and medial prefrontal cortex (mPFC) (Reul and de Kloet, 1985; de Kloet et al., 1986; Van Eekelen et al., 1988). Given the localization of GRs receptors, memory impairments induced by exposure to a stressor or glucocorticoids (GCs) are mainly correlated to altered plasticity into the hippocampus, the amygdala and the prefrontal cortex (Maroun and Richter-Levin, 2003; Jay et al., 2004; Vouimba et al., 2004; Sandi et al., 2005). "
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    ABSTRACT: Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC) and the hippocampus (dHPC) in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each) delivered before memory testing reversed the memory retrieval pattern (MRP) in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non-stress condition) to mPFC-dependent MRP and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.
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