Early-life stress induces EAAC1 expression reduction and attention-deficit and depressive behaviors in adolescent rats

Kim, Han Byeol; Yoo, Ji Young; Yoo, Seung Seok; Suh, Sang Won; Lee, Seoul; Park, Ji Hye; Lee, Jun Ho; Baik, Tai-Kyoung; Kim, Hye Sun; Woo, Ran-Sook

doi:10.1038/s41420-020-00308-9

Cited by 9 publications

(7 citation statements)

References 69 publications

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“…There is also evidence suggesting that ELA, specifically MS, may have a delayed impact on PV cell density. Brains that were collected immediately (or within a few days) after ELA experience generally had no significant differences in PV levels compared to control-rearing (Giachino et al, 2007 ; Brenhouse and Andersen, 2011 ; Soares et al, 2020 ; Richardson et al, 2021 ), while brains collected later in life (in adolescence and/or P40 and older) generally had decreased PV levels (Leussis et al, 2012 ; Wieck et al, 2013 ; Ganguly et al, 2015 ; Lukkes et al, 2017 , 2018 ; Kim et al, 2020 ; Aksic et al, 2021 ). Since PV cells have been found to increase significantly in number from juvenility to adolescence in brain regions such as the PFC (Caballero et al, 2014 ; Wu et al, 2014 ), it is possible that ELA may inhibit the maturational time course of PV cells.…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in Affective Dysfunction and Alterations in Parvalbumin in Rodent Models of Early Life Adversity

Ellis

Ganguly

2021

Front. Behav. Neurosci.

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The early life environment markedly influences brain and behavioral development, with adverse experiences associated with increased risk of anxiety and depressive phenotypes, particularly in females. Indeed, early life adversity (ELA) in humans (i.e., caregiver deprivation, maltreatment) and rodents (i.e., maternal separation, resource scarcity) is associated with sex-specific emergence of anxious and depressive behaviors. Although these disorders show clear sex differences in humans, little attention has been paid toward evaluating sex as a biological variable in models of affective dysfunction; however, recent rodent work suggests sex-specific effects. Two widely used rodent models of ELA approximate caregiver deprivation (i.e., maternal separation) and resource scarcity (i.e., limited bedding). While these approaches model aspects of ELA experienced in humans, they span different portions of the pre-weaning developmental period and may therefore differentially contribute to underlying mechanistic risk. This is borne out in the literature, where evidence suggests differences in trajectories of behavior depending on the type of ELA and/or sex; however, the neural underpinning of these differences is not well understood. Because anxiety and depression are thought to involve dysregulation in the balance of excitatory and inhibitory signaling in ELA-vulnerable brain regions (e.g., prefrontal cortex, amygdala, hippocampus), outcomes are likely driven by alterations in local and/or circuit-specific inhibitory activity. The most abundant GABAergic subtypes in the brain, accounting for approximately 40% of inhibitory neurons, contain the calcium-binding protein Parvalbumin (PV). As PV-expressing neurons have perisomatic and proximal dendritic targets on pyramidal neurons, they are well-positioned to regulate excitatory/inhibitory balance. Recent evidence suggests that PV outcomes following ELA are sex, age, and region-specific and may be influenced by the type and timing of ELA. Here, we suggest the possibility of a combined role of PV and sex hormones driving differences in behavioral outcomes associated with affective dysfunction following ELA. This review evaluates the literature across models of ELA to characterize neural (PV) and behavioral (anxiety- and depressive-like) outcomes as a function of sex and age. Additionally, we detail a putative mechanistic role of PV on ELA-related outcomes and discuss evidence suggesting hormone influences on PV expression/function which may help to explain sex differences in ELA outcomes.

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Section: Introductionmentioning

confidence: 99%

Sex Differences in Affective Dysfunction and Alterations in Parvalbumin in Rodent Models of Early Life Adversity

Ellis

Ganguly

2021

Front. Behav. Neurosci.

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“…Findings of decreased PV cell numbers in CA1, CA2, CA4, and the parasubiculum in individual studies have been countered by findings of no change in PV cell numbers across hippocampal subregions ( Chu et al., 2016 ; Knable et al., 2004 ; Pantazopoulos et al., 2010 ; Wang et al., 2011 ). The entorhinal cortex, despite one null report ( Kim et al., 2020 ), had lower PV cell density in two studies ( Pantazopoulos et al., 2010 ; Wang et al., 2011 ). Individual studies have examined BA24 and the thalamic reticular nucleus (TRN) of BD patients and found increased clustering but unchanged density of PV cells in BA24 ( Cotter et al., 2002 ) and decreased total PV cell number in the TRN of BD patients ( Steullet et al., 2018 ).…”

Section: Resultsmentioning

confidence: 79%

“…There was little evidence of changes in mRNA or protein in the whole hippocampus ( Banasr et al., 2017 ; Bath et al., 2016 ; Brenhouse and Andersen, 2011 ; Kim et al., 2020 ; Lussier and Stevens, 2016 ; Rossetti et al., 2018 ; Ueno et al., 2018 ) or in its subregions ( Clarke et al., 2019 ; Krugers et al., 1996 ; Nowak et al., 2010 ; Soares et al., 2020 ) and the studies showing an effect reported mixed directionality ( Bath et al., 2016 ; Kim et al., 2020 ; Lussier and Stevens, 2016 ; Riga et al., 2017 ; Rossetti et al., 2018 ; Ueno et al., 2017 ). The few studies including enrichment paradigms showed contradictory effects ( Donato et al., 2013 ; Gomes da Silva et al., 2010 ; Kong et al., 2017 ; McHugh et al., 2009 ; Prévot and Sibille, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…However, another MS study found increased staining for the oxidative stress marker 8-oxo-dG in dentate, CA1 and CA2/3 PV cells of juvenile females than males ( Soares et al., 2020 ). Two MS studies reported no sex difference in PV cell density, immunoreactive number, or protein expression in the whole HC ( Katahira et al., 2018 ; Kim et al., 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…(2017) Mouse (CD1) Early postnatal Early postnatal, juvenile ♂♀ 24 h MS on P4 with no food or water Dorsal Hippocampus IHC PV cell density decreased in left but not right dorsal hippocampus at both P14 and P28 [78] Katahira et al. (2018) Rat (Sprague-Dawley) Early postnatal Juvenile, adolescent ♂ MS 4h/day from P2–P20 Hippocampus IHC; Western blot PV cell density; PV protein content no change [19] Brenhouse and Andersen (2011) Rat (Sprague-Dawley) Early postnatal Adolescent ♂♀ MS 3h/day 3 weeks Hippocampus IHC; Western blot PV immunoreactivity; PV cluster number; PV protein expression decreased immunoreactivity and cluster number [80] Kim et al. (2020) GAD67-GFP Mouse (CD1) – Juvenile, adult ♂ Maternal stress: beginning on GD12, mothers received restraint stress 45 min 3x/d during daylight under bright lights.…”

Section: Resultsmentioning

confidence: 99%

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Parvalbumin interneuron alterations in stress-related mood disorders: A systematic review

Perlman¹,

Tanti²,

Mechawar³

2021

Neurobiology of Stress

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Stress-related psychiatric disorders including depression involve complex cellular and molecular changes in the brain, and GABAergic signaling dysfunction is increasingly implicated in the etiology of mood disorders. Parvalbumin (PV)-expressing neurons are fast-spiking interneurons that, among other roles, coordinate synchronous neuronal firing. Mounting evidence suggests that the PV neuron phenotype is altered by stress and in mood disorders. In this systematic review, we assessed PV interneuron alterations in psychiatric disorders as reported in human postmortem brain studies and animal models of environmental stress. This review aims to 1) comprehensively catalog evidence of PV cell function in mood disorders (humans) and stress models of mood disorders (animals); 2) analyze the strength of evidence of PV interneuron alterations in various brain regions in humans and rodents; 3) determine whether the modulating effect of antidepressant treatment, physical exercise, and environmental enrichment on stress in animals associates with particular effects on PV function; and 4) use this information to guide future research avenues. Its principal findings, derived mainly from rodent studies, are that stress-related changes in PV cells are only reported in a minority of studies, that positive findings are region-, age-, sex-, and stress recency-dependent, and that antidepressants protect from stress-induced apparent PV cell loss. These observations do not currently translate well to humans, although the postmortem literature on the topic remains limited.

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“The wrong tools for the right job”: a critical meta-analysis of traditional tests to assess behavioural impacts of maternal separation

2022

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Rationale Unconditioned tasks in rodents have been the mainstay of behavioural assessment for decades, but their validity and sensitivity to detect the behavioural consequences of early life stress (ELS) remains contentious and highly variable. Objectives In the present study, we carried out a meta-analysis to investigate whether persistent behavioural effects, as assessed using unconditioned procedures in rats, are a reliable consequence of early repeated maternal separation, a commonly used procedure in rodents to study ELS. Methods A literature search identified 100 studies involving maternally separated rats and the following unconditioned procedures: the elevated plus maze (EPM); open field test (OFT); sucrose preference test (SPT) and forced swim task (FST). Studies were included for analysis if the separation of offspring from the dam was at least 60 min every day during the pre-weaning period prior to the start of adolescence. Results Our findings show that unconditioned tasks are generally poor at consistently demonstrating differences between control and separated groups with pooled effect sizes that were either small or non-existent (EPM: Hedge’s g = − 0.35, p = 0.01, OFT: Hedge’s g = − 0.32, p = 0.05, SPT: Hedge’s g = − 0.33, p = 0.21, FST: Hedge’s g = 0.99, p = 0.0001). Despite considerable procedural variability between studies, heterogeneity statistics were low; indicating the lack of standardization in the maternal separation protocol was the not the cause of these inconsistent effects. Conclusions Our findings indicate that in general, unconditioned tests of depression and anxiety are not sufficient to reveal the full behavioural repertoire of maternal separation stress should not be relied upon in isolation. We argue that more objective tasks that sensitively detect specific cognitive processes are better suited for translational research on stress-related disorders such as depression.

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Early-life stress induces EAAC1 expression reduction and attention-deficit and depressive behaviors in adolescent rats

Cited by 9 publications

References 69 publications

Sex Differences in Affective Dysfunction and Alterations in Parvalbumin in Rodent Models of Early Life Adversity

Sex Differences in Affective Dysfunction and Alterations in Parvalbumin in Rodent Models of Early Life Adversity

Parvalbumin interneuron alterations in stress-related mood disorders: A systematic review

“The wrong tools for the right job”: a critical meta-analysis of traditional tests to assess behavioural impacts of maternal separation

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