Repeated stress exposure in mid-adolescence attenuates behavioral, noradrenergic, and epigenetic effects of trauma-like stress in early adult male rats

Abstract Stress in adolescence can regulate vulnerability to traumatic stress in adulthood through region-specific epigenetic activity and catecholamine levels. We hypothesized that stress in adolescence would increase adult trauma vulnerability by impairing extinction-retention, a deficit in PTSD, by (1) altering class IIa histone deacetylases (HDACs), which integrate effects of stress on gene expression, and (2) enhancing norepinephrine in brain regions regulating cognitive effects of trauma. We investigated the effects of adolescent-stress on adult vulnerability to severe stress using the single-prolonged stress (SPS) model in male rats. Rats were exposed to either (1) adolescent-stress (33–35 postnatal days) then SPS (58–60 postnatal days; n = 14), or (2) no adolescent-stress and SPS (58–60 postnatal days; n = 14), or (3) unstressed conditions (n = 8). We then measured extinction-retention, norepinephrine, HDAC4, and HDAC5. As expected, SPS exposure induced an extinction–retention deficit. Adolescent-stress prior to SPS eliminated this deficit, suggesting adolescent-stress conferred resiliency to adult severe stress. Adolescent-stress also conferred region-specific resilience to norepinephrine changes. HDAC4 and HDAC5 were down-regulated following SPS, and these changes were also modulated by adolescent-stress. Regulation of HDAC levels was consistent with the pattern of cognitive effects of SPS; only animals exposed to SPS without adolescent-stress exhibited reduced HDAC4 and HDAC5 in the prelimbic cortex, hippocampus, and striatum. Thus, HDAC regulation caused by severe stress in adulthood interacts with stress history such that seemingly conflicting reports describing effects of adolescent stress on adult PTSD vulnerability may stem in part from dynamic HDAC changes following trauma that are shaped by adolescent stress history.

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Pairing of neonatal phencyclidine exposure and acute adolescent stress in male rats as a novel developmental model of schizophrenia

Behavioural Brain Research ◽

10.1016/j.bbr.2021.113308 ◽

2021 ◽

Vol 409 ◽

pp. 113308

Author(s):

Alexander A. Moghadam ◽

Linnea R. Vose ◽

Omid Miry ◽

Xiao-Lei Zhang ◽

Patric K. Stanton

Keyword(s):

Developmental Model ◽

Male Rats ◽

Adolescent Stress

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Corrigendum to: Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism [Int. J. Devl. Neurosci. 31 (2013) 311–318]

International Journal of Developmental Neuroscience ◽

10.1016/j.ijdevneu.2013.09.003 ◽

2013 ◽

Vol 31 (8) ◽

pp. 715-718

Author(s):

Wafaa A. Hassan ◽

Taghride Abdel Rahman ◽

Mona S. Aly ◽

Asmaa S. Shahat

Keyword(s):

Adult Male ◽

Brain Regions ◽

Male Rats ◽

Peripheral Tissues ◽

Experimental Hyperthyroidism

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Abstract P730: MCA Stroke Chronically Disrupts Hippocampal Activity and Cortico-Hippocampal Communication

Stroke ◽

10.1161/str.52.suppl_1.p730 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Zachary Ip ◽

Gratianne Rabiller ◽

Jiwei He ◽

Shivalika Chavan ◽

Yasuo Nishijima ◽

...

Keyword(s):

Structural Integrity ◽

Memory Function ◽

Brain Regions ◽

Male Rats ◽

Brain State ◽

Signal Power ◽

Hippocampal Function ◽

Electrode Arrays ◽

Mca Occlusion ◽

Hippocampal Activity

Introduction: Cognition and memory deficits are common sequelae following middle cerebral artery (MCA) stroke, one of the most common strokes in humans. However MCA stroke does not compromise the structural integrity of the hippocampus, which is highly involved in memory function, because the MCA does not supply blood flow to the hippocampus. We previously reported on the acute effect of MCA stroke, where we observed increased hippocampal activity and cortico-hippocampal communication. Here we investigate chronic changes to local oscillations and cortico-hippocampal communication following MCA occlusion in rats two weeks and one month following stroke. Hypothesis: Cortical stroke affects remote brain regions, disrupting hippocampal function and cortico-hippocampal communication. Methods: We subjected male rats (n=28) to distal MCA occlusion compared to controls (n=19). We recorded local field potentials simultaneously from cortex and hippocampus two weeks and one month following stroke using 16-site linear electrode arrays under urethane anesthesia. We analyzed signal power, brain state, CFC, and sharp wave SPW-Rs to assess hippocampal function and cortico-hippocampal communication. Results: Our results show disruptions to local oscillations; lowered delta (1-3 Hz) signal power in the cortex and hippocampus, increased signal power in gamma (30-60 Hz) and high gamma (60-200 Hz) in cortex and hippocampus. Theta/delta brain state is disrupted, and SPW-Rs increase in power at two weeks, before returning to baseline levels at one month. Communication is also disrupted; Theta-gamma coupling, a measure of information being communicated between regions, breaks down after stroke. Conclusions: These results suggest that chronic stroke causes significant changes to hippocampal function, which can be characterized by these electrophysiological biomarkers, establishing putative targets for targeted stimulation therapies.

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Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. II. Behavioral and Neurodevelopment Effects

International Journal of Toxicology ◽

10.1080/10915810500367094 ◽

2005 ◽

Vol 24 (6) ◽

pp. 451-467 ◽

Cited By ~ 11

Author(s):

Raymond G. York ◽

John Barnett ◽

Michael F. Girard ◽

David R. Mattie ◽

Marni V. K. Bekkedal ◽

...

Keyword(s):

Drinking Water ◽

Ammonium Perchlorate ◽

Brain Regions ◽

Male Rats ◽

Male Rat ◽

Sprague Dawley ◽

Continuous Access ◽

Brain Morphometry ◽

The Central Nervous System ◽

The Right

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

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Short- and long-term alterations of FKBP5-GR and specific microRNAs in the prefrontal cortex and hippocampus of male rats induced by adolescent stress contribute to depression susceptibility

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2018.11.008 ◽

2019 ◽

Vol 101 ◽

pp. 204-215 ◽

Cited By ~ 12

Author(s):

Jingjing Xu ◽

Rui Wang ◽

Yuan Liu ◽

Wei Wang ◽

Dexiang Liu ◽

...

Keyword(s):

Prefrontal Cortex ◽

Male Rats ◽

Adolescent Stress ◽

Short And Long Term

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Effects of early neonatal proinflammatory stress on the expression of BDNF transcripts in the brain regions of prepubertal male rats

Vavilov Journal of Genetics and Breeding ◽

10.18699/vj16.149 ◽

2016 ◽

Vol 20 (2) ◽

pp. 191-197

Author(s):

D. I. Peregud ◽

S. V. Freiman ◽

A. O. Tishkina ◽

L. S. Sokhranyaeva ◽

N. A. Lazareva ◽

...

Keyword(s):

Brain Regions ◽

Male Rats ◽

The Brain

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Thallium Induced Changes in Behavioral Patterns: Correlation With Altered Lipid Peroxidation and Lysosomal Enzyme Activity in Brain Regions of Male Rats

Toxicology and Industrial Health ◽

10.1177/074823378500100109 ◽

1985 ◽

Vol 1 (1) ◽

pp. 81-98 ◽

Cited By ~ 15

Author(s):

David R. Brown ◽

Barbara G. Callahan ◽

Mark A. Cleaves ◽

Robert A. Schatz

Keyword(s):

Lipid Peroxidation ◽

Lysosomal Enzyme ◽

Brain Regions ◽

Male Rats ◽

Patterns Of Behavior ◽

Low Levels ◽

Behavioral Sequelae ◽

Human Poisoning ◽

And Function ◽

Induced Changes

The effects of exposures to low levels of heavy metals is a complex and serious problem. Thallium is a metal which produces behavioral sequelae in human poisoning and is potentially hazardous with low level exposures. A test battery is presented which utilizes biochemical and behavioral testing to assess the effects of low levels of thallium on central nervous system chemistry and function in rats. The doses of thallium used (4 and 8 mg/kg) produced no overt signs of behavioral toxicity but did produce dose-related increases in lipid peroxidation and activation of the lysosomal enzyme beta-galactosidase in selected brain regions. At these dose levels, thallium also selectively altered the patterns of behavior. The study suggests that the target regions of thallium in the brain include the cortex, the cerebellum and the brainstem. The dose-response relationships, found for certain pairs of behavioral acts, were correlated with biochemical changes in one or more brain regions.

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Abstract WP288: Inter-Alpha Inhibitor Proteins Reduce the Presence of Neutrophils and Matrix Metalloproteinase-9 Positive Neutrophils in Damaged Brain Regions of Neonates with Hypoxic-Ischemic (HI) Brain Injury

Stroke ◽

10.1161/str.48.suppl_1.wp288 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Adriel Barrios-Anderson ◽

Xiaodi Chen ◽

Yow-Pin Lim ◽

Barbara S Stonestreet

Keyword(s):

Brain Injury ◽

Corpus Callosum ◽

Matrix Metalloproteinase ◽

Right Hemisphere ◽

Brain Regions ◽

Matrix Metalloproteinase 9 ◽

Male Rats ◽

Control Group ◽

Neonatal Rats ◽

Metalloproteinase 9

Introduction: Inter-alpha inhibitor proteins (IAIPs) are immunomodulatory proteins that play a significant anti-inflammatory role in hypoxic ischemic (HI) brain injury. We have shown that administering IAIPs after HI improves histopathological brain injury, brain weight, and behavioral outcomes in neonatal rats. Neutrophils are specialized leukocytes known to infiltrate the brain parenchyma and exacerbate neuronal injury after HI. One molecular mechanism by which neutrophils exert damage on the blood-brain barrier (BBB) and brain tissue after ischemia is by the release of matrix metalloproteinase-9 (MMP9), an enzyme that breaks down the extracellular matrices of surrounding cells. Objective: To determine the effect of IAIPs on neutrophil infiltration and release of MMP9 in neonatal rats after HI. Methods: The Vannucci model was used to induce neonatal HI in postnatal day 7 rats that were assigned to a Non-ischemic sham-control group (Sham, n=12), right-sided carotid ligation with exposure to hypoxia (8% oxygen for 90 min) treated with placebo group (PL-HI, n=17), or an IAIP treated group (IAIP-HI, n=17). Rat sex was recorded. IAIP (30 mg/kg) or PL was given intraperitoneally at 0, 24 and 48 h after HI. We removed the rat brain after 72h and performed immunohistochemistry using MPO (neutrophil selective) and MMP9 fluorescent markers. We performed stereological analyses with the StereoInvestigator 10.0 Fractionator probe without knowledge of group assignment to quantify neutrophils and MMP9 positive cells present within the right hemisphere, cortex, corpus callosum, and hippocampus. Results: MPO positive cells were significantly reduced in male IAIP treated rats compared with PL-HI in the overall damaged hemisphere (p<0.01) and the corpus callosum (p<0.05). Further, we observed MPO and MMP9 co-localization, and IAIP treatment reduced the presence of MMP9 positive neutrophils in the cortex of male rats compared to placebo (P<0.05).

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