Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule

Borcel, Érika; Pérez-Álvarez, Laura; Herrero, Ana; Brionne, Thomas C.; Varea, Emilio; Berezin, Vladimir; Bock, Elisabeth; Sandi, Carmen; Venero, César

doi:10.1097/fbp.0b013e3282f3fca9

Cited by 65 publications

(47 citation statements)

References 46 publications

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“…NCAMmimicking peptides are being developed for their potential efficacy [69,70], although the therapeutic efficacy of these NCAM-peptide mimetics remains to be tested. In a recent study the ability of C3d, a NCAM mimetic peptide, to promote ChAT activity in septal cholinergic neurons was reported [71].…”

Section: Discussionmentioning

confidence: 99%

Altered NCAM Expression Associated with the Cholinergic System in Alzheimer's Disease

Aisa

Gil-Bea

Solas

et al. 2010

JAD

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Abstract. Neurotransmitter system dysfunction and synapse loss have been recognized as hallmarks of Alzheimer's disease (AD). Our hypothesis is that specific neurochemical populations of neurons might be more vulnerable to degeneration in AD due to particular deficits in synaptic plasticity. We have studied, in postmortem brain tissue, the relationship between levels of synaptic markers (NCAM and BDNF), neurochemical measurements (cholinacetyltransferase activity, serotonin, dopamine, GABA, and glutamate levels), and clinical data (cognitive status measured as MMSE score). NCAM levels in frontal and temporal cortex from AD patients were significantly lower than control patients. Interestingly, these reductions in NCAM levels were associated to an ApoE4 genotype. Levels of BDNF were also significantly reduced in both frontal and temporal regions in AD patients. The ratio between plasticity markers and neurochemical measurements was used to study which of the neurochemical populations was particularly associated to plasticity changes. In both the frontal and temporal cortex, there was a significant reduction in the ChAT/NCAM ratio in AD samples compared to controls. None of the ratios to BDNF were different between control and AD samples. Furthermore, Pearson's product moment showed a significant positive correlation between MMSE score and the ChAT/NCAM ratio in frontal cortex (n = 19; r = 0.526*; p = 0.037) as well as in temporal cortex (n = 19; r = 0.601*; p = 0.018) in AD patients. Altogether, these data suggest a potential involvement of NCAM expressing neurons in the cognitive deficits in AD.

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Section: Discussionmentioning

confidence: 99%

Altered NCAM Expression Associated with the Cholinergic System in Alzheimer's Disease

Aisa

Gil-Bea

Solas

et al. 2010

JAD

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“…It might be suggested that facilitating NCAM function--particularly the NCAM-140 isoform--might represent a new alternative to overcome stressinduced neural alterations. NCAM-mimicking peptides are being developed for their potential efficacy in modulating NCAM function, and thereby in treating neural and cognitive disorders Borcel et al, 2008), although the therapeutic efficacy of these NCAM-peptide mimetics on stress-related disorders remains to be tested.…”

Section: Figurementioning

confidence: 99%

Effects of neonatal stress on markers of synaptic plasticity in the hippocampus: Implications for spatial memory

et al. 2009

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Early stressful adverse situations may increase the vulnerability to cognitive deficits and psychiatric disorders, such as depression. Maternal separation (MS) has been used as an animal model to study changes in neurochemistry and behavior associated with exposure to early-life stress. This study investigated the effects of neonatal stress (MS) on the expression of synaptic plasticity markers in the hippocampus and a purported relationship to cognitive processes. Spatial learning (Morris water maze) significantly increased the expression of total levels of the neural cell adhesion molecule (NCAM), as well as its three major isoforms (NCAM-120, -140, and -180) both in the control and MS groups. Interestingly, these increases in NCAM expression after learning were lower in MS animals when compared with control rats. MS induced a significant decrease in total levels of NCAM, and specifically, in the NCAM-140 isoform expression. In the hippocampus of MS rats there was a significant decrease in brain-derived neurotrophic factor and synaptophysin mRNA densities. Cell proliferation, measured as BrdU-positive cells, was also decreased in the dentate gyrus of MS rats. Altogether these results suggest that MS can alter normal brain development, providing a potential mechanism by which early environmental stressors may influence vulnerability to show cognitive impairments later in life.

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“…While present, these changes have functional implications, such as impaired memory (centered on the hippocampus; Borcel et al 2008). Such functional changes are generally reversible after an acute stressor.…”

Section: Structural Effectsmentioning

confidence: 99%

“…A major stress-induced outcome in these areas is decreased neuronal numbers, in which two mechanisms have been implicated (Czeh et al 2007;Fuchs, Flugge, and Czeh 2006;Lucassen et al 2006). The first is decreased neuron production, which may occur during either initial development (Card et al 2005;Korosi et al 2012) or in the course of adult brain remodeling (Borcel et al 2008;Czeh et al 2007;Danzer 2012;Fuchs, Flugge, and Czeh 2006;Joca, Ferreira, and Guimaraes 2007;Lyons et al 2010;Yan et al 2011). The second mechanism is increased neuronal apoptosis (Lucassen et al 2006).…”

Section: Structural Effectsmentioning

confidence: 99%

Interpreting Stress Responses during Routine Toxicity Studies

et al. 2013

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Stress often occurs during toxicity studies. The perception of sensory stimuli as stressful primarily results in catecholamine release and activation of the hypothalamic-pituitary-adrenal (HPA) axis to increase serum glucocorticoid concentrations. Downstream effects of these neuroendocrine signals may include decreased total body weights or body weight gain; food consumption and activity; altered organ weights (e.g., thymus, spleen, adrenal); lymphocyte depletion in thymus and spleen; altered circulating leukocyte counts (e.g., increased neutrophils with decreased lymphocytes and eosinophils); and altered reproductive functions. Typically, only some of these findings occur in a given study. Stress responses should be interpreted as secondary (indirect) rather than primary (direct) test article-related findings. Determining whether effects are the result of stress requires a weight-of-evidence approach. The evaluation and interpretation of routinely collected data (standard in-life, clinical pathology, and anatomic pathology endpoints) are appropriate and generally sufficient to assess whether or not changes are secondary to stress. The impact of possible stress-induced effects on data interpretation can partially be mitigated by toxicity study designs that use appropriate control groups (e.g., cohorts treated with vehicle and subjected to the same procedures as those dosed with test article), housing that minimizes isolation and offers environmental enrichment, and experimental procedures that minimize stress and sampling and analytical bias.This article is a comprehensive overview of the biological aspects of the stress response, beginning with a Summary (Section 1) and an Introduction (Section 2) that describes the historical and conventional methods used to characterize acute and chronic stress responses. These sections are followed by reviews of the primary systems and parameters that regulate and/or are influenced by stress, with an emphasis on parameters evaluated in toxicity studies:

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Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule

Cited by 65 publications

References 46 publications

Altered NCAM Expression Associated with the Cholinergic System in Alzheimer's Disease

Altered NCAM Expression Associated with the Cholinergic System in Alzheimer's Disease

Effects of neonatal stress on markers of synaptic plasticity in the hippocampus: Implications for spatial memory

Interpreting Stress Responses during Routine Toxicity Studies

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