Maternal separation induces hippocampal changes in cadherin-1 (CDH-1) mRNA and recognition memory impairment in adolescent mice

Azeredo, Lucas Araújo de; Wearick-Silva, Luís Eduardo; Viola, Thiago Wendt; Tractenberg, Saulo Gantes; Centeno-Silva, Anderson; Orso, Rodrigo; Schröder, Nadja; Bredy, Timothy W.; Grassi‐Oliveira, Rodrigo

doi:10.1016/j.nlm.2017.04.006

Cited by 21 publications

(19 citation statements)

References 82 publications

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“…Our findings revealed that, as expected, MS led to impaired working memory and reference memory in 8-RAM considering the number of total errors committed along all testing days. This result is consistent with prior studies showing that different ELS models can disrupt working memory and memory processes (i.e., consolidation and retrieval processes), through functional alterations of specific brain regions (Cattaneo et al, 2019;Chocyk et al, 2013;de Azeredo et al, 2017;Grassi-Oliveira et al, 2016;Jin et al, 2013;van der Kooij, Grosse, Zanoletti, Papilloud, & Sandi, 2015;Liu, Atrooz, Salvi, & Salim, 2017;Mehta & Schmauss, 2011). However, not all MS animals presented the same pattern of cognitive performance.…”

Section: Discussionsupporting

confidence: 92%

“…One of the core aspects of this high-risk neuropsychiatric profile is related to the adverse effects of early life stress (ELS) on neurodevelopment and the persistent structural and functional changes in central brain regions such as the prefrontal cortex (PFC) and the hippocampus (Hipp). These regions were commonly found to be significantly impaired in both human (De Bellis, Hooper, Spratt, & Woolley, 2009;Mothes et al, 2015;Navalta, Polcari, Webster, Boghossian, & Teicher, 2006;Nikulina & Widom, 2013;Oswald et al, 2014) and animal (Aisa et al, 2009;Chocyk et al, 2013;de Azeredo et al, 2017;Grassi-Oliveira, Honeycutt, Holland, Ganguly, & Brenhouse, 2016;Reincke & Hanganu-Opatz, 2017) studies, addressing the effects of ELS later in life.…”

Section: Introductionmentioning

confidence: 99%

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Vulnerable and resilient cognitive performance related to early life stress: The potential mediating role of dopaminergic receptors in the medial prefrontal cortex of adult mice

Tractenberg

Orso

Creutzberg

et al. 2020

Intl J of Devlp Neuroscience

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Rationale Exposure to early life stress (ELS) is known to have pronounced effects on the prefrontal cortex (PFC). However, not all individuals exposed to ELS manifest the same neurobiological and cognitive phenotypes when adults. Dopamine signaling could be a key factor in understanding the effects of stress on PFC‐related cognitive function. Objectives We aimed to investigate the differential effects of ELS on cognitive performance of adult mice and the dopaminergic receptors expression in the PFC. Methods BALB/c males were exposed to the maternal separation (MS) procedure and their cognitive performance on the eight‐arm radial maze (8‐RAM) were assessed during adulthood. For molecular‐level assessments, we performed mRNA expression analyses for dopamine receptors—DRD1, DRD2, DRD3—and Hers1 expression in the medial PFC. Results While MS produced an overall impairment on 8‐RAM, the stressed animals could be divided in two groups based on their performance: those with impaired cognitive performance (vulnerable to maternal separation, V‐MS) and those without any impairment (resilient to maternal separation, R‐MS). V‐MS animals showed increased DRD1 and DRD2 expression in comparison with other groups. Errors on 8‐RAM were also positively correlated with DRD1 and DRD2 mRNA expression. Conclusions Our findings suggest a potential role of the dopaminergic system in the programming mechanisms of cognitive vulnerability and resilience related to ELS.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Vulnerable and resilient cognitive performance related to early life stress: The potential mediating role of dopaminergic receptors in the medial prefrontal cortex of adult mice

Tractenberg

Orso

Creutzberg

et al. 2020

Intl J of Devlp Neuroscience

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“…It is important to note that environmental interventions on a DISC1 mutation background did not significantly disrupt the results of the working memory task when compared to DISC1 animals without interventions. These results demonstrate that working memory is affected in all the control animal groups with various environmental interventions, exhibiting the effect of these stressors on the hippocampus (Malhotra et al, 1997;de Azeredo et al, 2017). Percent novel arm entries did not show any significant difference among control vs. intervention groups (data not shown).…”

Section: Y Maze: As An Index Of Working Memorymentioning

confidence: 63%

Expression of Behavioral Phenotypes in Genetic and Environmental Mouse Models of Schizophrenia

Sultana

Lee

2020

Front. Behav. Neurosci.

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Schizophrenia is a neuropsychiatric disorder characterized by multifactorial etiology involving complex interactions among genetic and environmental factors. "Multiplehit" models of the disorder can explain its variable incidence and prevalence in related individuals. Hence, there is a dire need to understand these interactions in the emergence of schizophrenia. To test these factors in the emergence of schizophrenia-like behaviors, we employed a genetic mouse model of the disorder (harboring the DISC1 mutation) along with various environmental insults, such as early life stress (maternal separation of pups) and/or pharmacological interventions (ketamine injections). When assessed on a battery of behavioral tests, we found that environmental interventions affect the severity of behavioral phenotypes in terms of increased negative behavior, as shown by reduced mobility in the forced swim and tail suspension tests, and changes to positive and cognitive symptoms, such as increased locomotion and disrupted PPI along with reduced working memory, respectively. Among the various interventions, the genetic mutation had the most profound effect on behavioral aberrations, followed by an environmental intervention by ketamine injections and ketamine-injected animals that were maternally separated during early postnatal days. We conclude that although environmental factors increased the prevalence of aberrant behavioral phenotypes, genetic background is still the predominant influence on phenotypic alterations in these mouse models of schizophrenia.

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“…Many of the genes found to be differentially expressed in the adrenal gland following stress exposure in this study have previously been reported to be stress-sensitive (33,34). All of the genes included in the SSGE index (Table 1) have been implicated in the response to stress in one or more tissues (35)(36)(37)(38)(39)(40)(41)(42)(43). Currently, however, relatively little is known about the specific role that these genes might play in mediating the response to stress in the adrenal gland.…”

Section: Discussionmentioning

confidence: 78%

“…Changes in expression of genes implicated in lipid metabolism and transport in the adrenal gland may indicate a long-term effect of stress on steroid hormone biosynthesis. Expression of Cadherin-8 (Cdh8) is decreased in the prefrontal cortex in response to stress and it has been hypothesized that this may alter tissue plasticity to favor adaptive synapse remodeling (43). The Na/H exchanger (Slc9a3) uses an inward sodium ion gradient to expel acids from the cell (46).…”

Section: Discussionmentioning

confidence: 99%

Universal Transcriptional Responses to Different Modalities of Traumatic Stress as a Measure of Stress Exposure

Rosati

et al. 2017

Preprint

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Molecular diagnostic tools that can robustly and quantitatively measure the response to traumatic stress would be of considerable value in assessing the individual risk of developing post-traumatic stress disorder or stress-induced depression following stress exposure. The gene regulatory network can integrate and encode a large number of different signals, including those elicited by exposure to stress. We find that many genes respond to at least one modality of stress but only a subset of stress-sensitive genes track stress exposure across multiple stress modalities and are thus universal markers of stress exposure. A sensitive and robust measure of stress exposure can be constructed using a small number of genes selected from this modality-independent set of stress-sensitive genes. This stress-sensitive gene expression (SSGE) index can detect chronic traumatic stress exposure in a wide range of different stress models in a manner that is relatively independent of the modality of stress exposure and that parallels the intensity of stress exposure in a dose-dependent manner.All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Maternal separation induces hippocampal changes in cadherin-1 (CDH-1) mRNA and recognition memory impairment in adolescent mice

Cited by 21 publications

References 82 publications

Vulnerable and resilient cognitive performance related to early life stress: The potential mediating role of dopaminergic receptors in the medial prefrontal cortex of adult mice

Vulnerable and resilient cognitive performance related to early life stress: The potential mediating role of dopaminergic receptors in the medial prefrontal cortex of adult mice

Expression of Behavioral Phenotypes in Genetic and Environmental Mouse Models of Schizophrenia

Universal Transcriptional Responses to Different Modalities of Traumatic Stress as a Measure of Stress Exposure

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