Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multi-modal stress

Maras, Pamela M.; Molet, Jenny; Chen, Y; Rice, Courtney J.; Ji, Sunggoan; Solodkin, Ana; Baram, TZ

doi:10.1038/mp.2014.64

Cited by 14 publications

(10 citation statements)

References 119 publications

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“…Following significant interactions, data were analyzed using Tukey’s post hoc tests. Differences in functional networks between brain regions were quantified by correlating c-Fos expression between interconnected brain regions and then the correlations were statistically compared between drug- and vehicle-treated groups, as previously described (Maras et al, 2014; Dwyer and Leslie, 2016; Wiersielis et al, 2016). All brain regions that share anatomical connections were correlated (Pearson’s product moment correlations) and compared using Fisher’s r to z transformations.…”

Section: Methodsmentioning

confidence: 99%

Sex- and Age-dependent Effects of Orexin 1 Receptor Blockade on Open-Field Behavior and Neuronal Activity

et al. 2018

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Adolescence is a sensitive and critical period in brain development where psychiatric disorders such as anxiety, depression and post-traumatic stress disorder are more likely to emerge following a stressful life event. Females are two times more likely to suffer from psychiatric disorders than males. Patients with these disorders show alterations in orexins (also called hypocretins), important neuropeptides that regulate arousal, wakefulness and the hypothalamic-pituitary-adrenal axis activity. Little is known on the role of orexins in mediating arousal behaviors in male and female rats during adolescence or adulthood. Here, we examine the influence of orexin 1 receptor blockade by SB334867 in open-field behavior in male and female rats during early adolescence (PND 31-33) or adulthood (PND 75-77). Animals were injected with 0 (vehicle), 1, 10, or 30 mg/kg SB334867 (i.p.). Thirty minutes later, they were placed in an open field, and behavior and neuronal activity (c-Fos) were assessed. In adolescent males, SB334867 significantly increased immobility in the 10 mg/kg group compared to vehicle. However, this increase in immobility in adolescent males was not observed in adolescent females. In contrast to adolescent males, adult males in the 10 mg/kg dose group showed the opposite effect on immobility compared to vehicle. These results indicate that 10 mg/kg dose of SB334867 has opposing effects in adolescent and adult males, but few effects in adolescent and adult females. Differences in functional networks between limbic regions may underlie these effects of orexin receptor blockade that are sex- and age-dependent in rats.

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Section: Methodsmentioning

confidence: 99%

Sex- and Age-dependent Effects of Orexin 1 Receptor Blockade on Open-Field Behavior and Neuronal Activity

et al. 2018

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“…In these areas, behavioral stress has been recognized as a powerful modifier of neuronal structural plasticity (McEwen et al, 2012 ; Chattarji et al, 2015 ). Either acute or chronic stress can transiently or stably modify dendritic spine density and arborization (Golden et al, 2013 ; Maras et al, 2014 ; Chattarji et al, 2015 ; Janak and Tye, 2015 ), suggesting that adaptive structural modification of corticolimbic areas can also correspond to a neutral behavioral response. The magnitude and direction of stress-mediated neuroplastic remodeling vary according to the peculiar structure observed, generally increasing amygdalar neuroplasticity (enhancing fear reactions) and decreasing hippocampal and prefrontal cortex functionality (leading to impaired control over affective manifestation; McEwen et al, 2012 ; Felix-Ortiz et al, 2013 ; Chattarji et al, 2015 ).…”

Section: Stress Impacts Neuronal Connectivity and Plasticitymentioning

confidence: 99%

Acute Stress-Induced Epigenetic Modulations and Their Potential Protective Role Toward Depression

Rusconi

Battaglioli

2018

Front. Mol. Neurosci.

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Psychiatric disorders entail maladaptive processes impairing individuals’ ability to appropriately interface with environment. Among them, depression is characterized by diverse debilitating symptoms including hopelessness and anhedonia, dramatically impacting the propensity to live a social and active life and seriously affecting working capability. Relevantly, besides genetic predisposition, foremost risk factors are stress-related, such as experiencing chronic psychosocial stress—including bullying, mobbing and abuse—, and undergoing economic crisis or chronic illnesses. In the last few years the field of epigenetics promised to understand core mechanisms of gene-environment crosstalk, contributing to get into pathogenic processes of many disorders highly influenced by stressful life conditions. However, still very little is known about mechanisms that tune gene expression to adapt to the external milieu. In this Perspective article, we discuss a set of protective, functionally convergent epigenetic processes induced by acute stress in the rodent hippocampus and devoted to the negative modulation of stress-induced immediate early genes (IEGs) transcription, hindering stress-driven morphostructural modifications of corticolimbic circuitry. We also suggest that chronic stress damaging protective epigenetic mechanisms, could bias the functional trajectory of stress-induced neuronal morphostructural modification from adaptive to maladaptive, contributing to the onset of depression in vulnerable individuals. A better understanding of the epigenetic response to stress will be pivotal to new avenues of therapeutic intervention to treat depression, especially in light of limited efficacy of available antidepressant drugs.

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“…Intriguingly the SHRP (postnatal day 2-9) largely overlaps with the temporal window during which NG2 cells reach their peak density (first postnatal week), and when the majority of divided NG2 cells differentiate into oligodendrocytes (33). ELS is capable to override the SHRP and to elicit a significant stress response with increased expression of central corticotropin releasing hormone and circulating corticosterone (CORT) concentrations, which in turn cause detrimental long lasting effect on memory formation and hippocampus-dependent cognitive functions (34)(35)(36). Still, the individual contribution of an ELS-induced CORT excess and the concomitant activation of central stress neurocircuits on the developing brain has not been finally dissected.…”

Section: Main Text Introductionmentioning

confidence: 99%

Early life stress programming of NG2+ glia transcriptome alters functional properties of voltage gated sodium (Nav) channels and cognitive performance

Treccani

Yiğit

Lingner

et al. 2020

Preprint

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Background: The detrimental effects of early adversity on brain development and adult mental health are well established. While studies have identified myelination processes and oligodendrocytes as targets of early adversity across species, knowledge about the precise molecular mechanisms and cell populations involved is still lacking. NG2+ cells are oligodendrocyte precursor cells with unique properties, as they form synapses with neurons, engage in cell-cell communication and respond to stress hormones. Methods: Using an established mouse model of early life stress (ELS) we performed cell-type specific molecular profiling in hippocampal NG2 cells at early postnatal and adult stages. To further dissect the impact of glucocorticoids on ELS-induced transcriptional changes, we integrated our data with available Chip-seq data on genomic binding sites of the glucocorticoid receptor (GR). The functional relevance of one candidate gene, Scn7a, was confirmed by electrophysiological recordings in hippocampal NG2 cells. Results: ELS specifically targeted the hippocampal NG2 cell transcriptome, and the molecular changes correlated with the ELS-induced increase of corticosterone. The overlap analysis with Chip-seq data on genomic binding sites of the GR revealed nine overlapping genes. Among those Scn7a, coding for a subunit of sodium channels, remained upregulated until adulthood in ELS animals. Upregulation of Scn7a was accompanied by an increase in the density of voltage-gated sodium channel activated currents in hippocampal NG2 cells. Conclusions: Our findings indicate that ELS specifically targets the transcriptional profiles and electrophysiological properties of hippocampal NG2 glia. Considering that voltage-gated sodium channels are important for the NG2 cell-to-neuron communication, our findings may provide novel insights into the pathophysiological processes underlying stress related mental disorders.

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Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multi-modal stress

Cited by 14 publications

References 119 publications

Sex- and Age-dependent Effects of Orexin 1 Receptor Blockade on Open-Field Behavior and Neuronal Activity

Sex- and Age-dependent Effects of Orexin 1 Receptor Blockade on Open-Field Behavior and Neuronal Activity

Acute Stress-Induced Epigenetic Modulations and Their Potential Protective Role Toward Depression

Early life stress programming of NG2+ glia transcriptome alters functional properties of voltage gated sodium (Nav) channels and cognitive performance

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