scholarly journals Juvenile exposure to acute traumatic stress leads to long-lasting alterations in grey matter myelination in adult female but not male rats

2020 ◽  
Author(s):  
Jocelyn M Breton ◽  
Matthew Barraza ◽  
Kelsey Y Hu ◽  
Samantha Joy Frias ◽  
Kimberly L.P. Long ◽  
...  
Keyword(s):  
Traumatic Stress ◽  
Grey Matter ◽  
Acute Stress ◽  
Brain Regions ◽  
Adult Brain ◽  
Female Rats ◽  
Male Rats ◽  
Stress Exposure ◽  
Corticosterone Release

Stress early in life can have a major impact on brain development, and there is increasing evidence that childhood stress confers vulnerability for later developing psychiatric disorders. In particular, during peri-adolescence, brain regions crucial for emotional regulation, such as the prefrontal cortex (PFC), amygdala (AMY) and hippocampus (HPC), are still developing and are highly sensitive to stress. Changes in myelin levels have been implicated in mental illnesses and stress effects on myelin and oligodendrocytes (OLs) are beginning to be explored as a novel and underappreciated mechanism underlying psychopathologies. Yet there is little research on the effects of acute stress on myelin during peri-adolescence, and even less work exploring sex-differences. Here, we used a rodent model to test the hypothesis that exposure to acute traumatic stress as a juvenile would induce changes in OLs and myelin content across limbic brain regions. Male and female juvenile rats underwent three hours of restraint stress with exposure to a predator odor on postnatal day (p) 28. Acute stress induced a physiological response, increasing corticosterone release and reducing weight gain in stress-exposed animals. Brain sections containing the PFC, AMY and HPC were taken either in adolescence (p40), or in adulthood (p95) and stained for markers of OLs and myelin. We found that acute stress induced sex-specific changes in grey matter (GM) myelination and OLs in both the short- and long-term. Exposure to a single stressor as a juvenile increased GM myelin content in the AMY and HPC in p40 males, compared to the respective control group. At p40, corticosterone release during stress exposure was also positively correlated with GM myelin content in the AMY of male rats. Single exposure to juvenile stress also led to long-term effects exclusively in female rats. Compared to controls, stress-exposed females showed reduced GM myelin content in all three brain regions. Acute stress exposure decreased PFC and HPC OL density in p40 females, perhaps contributing towards this observed long-term decrease in myelin content. Overall, our findings suggest that the juvenile brain is vulnerable to exposure to a brief severe stressor. Exposure to a single short traumatic event during peri-adolescence produces long-lasting changes in GM myelin content in the adult brain of female, but not male, rats. These findings highlight myelin plasticity as a potential contributor to sex-specific sensitivity to perturbation during a critical window of development.

scholarly journals Region-specific maladaptive gray matter myelination is associated with differential susceptibility to stress-induced behavior in male rodents and humans

2021 ◽  
Author(s):  
Kimberly L. P. Long ◽  
Linda L. Chao ◽  
Yurika Kazama ◽  
Anjile An ◽  
Kelsey Y. Hu ◽  
...  
Keyword(s):  
Gray Matter ◽  
Traumatic Stress ◽  
Adult Brain ◽  
Fear Learning ◽  
Male Rats ◽  
Adult Rats ◽  
Behavioral Variation ◽  
Weighted Estimates ◽  
Functional Changes ◽  
Symptom Profiles

AbstractBackgroundIndividual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies have demonstrated surprising plasticity of oligodendrocytes and myelin in the adult brain, providing a potential mechanism by which aberrant structural and functional changes arise in the brain following trauma exposure.MethodsWe tested the hypothesis that gray matter myelin contributes to traumatic stress-induced behavioral variation. We exposed adult rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior. We quantified oligodendrocyte and myelin content in multiple brain areas and compared these measures to behavioral metrics. We then induced overexpression of the oligodendrogenic transcription factor Olig1 in the adult rat dentate gyrus (DG) to test the potential, causal role of oligodendrogenesis in behavioral variation. Lastly, T1-/T2-weighted estimates of myelin were compared to trauma-induced symptom profiles in humans.ResultsOligodendrocytes and myelin in the DG of the hippocampus positively correlated with stress-induced avoidance behaviors in male rats. In contrast, myelin levels in the amygdala positively correlated with contextual fear learning. Olig1 overexpression increased place avoidance compared to control virus animals, indicating that increased oligodendrocyte drive in the DG is sufficient to induce an avoidance behavioral phenotype. Finally, variation in myelin correlated with trauma-induced symptom profiles in humans in a region-specific manner that mirrored our rodent findings.ConclusionsThese results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and myelin and differential behavioral phenotypes following traumatic stress exposure. This study provides a novel biological framework for understanding the mechanisms that underlie individual variance in sensitivity to traumatic stress.

scholarly journals Long-term effect of diet amended by risk elements contaminated soils on risk element penetration and physiological parameters of rats

2014 ◽  
Vol 59 (No. 9) ◽  
pp. 416-427
Author(s):  
V. Vlčková ◽  
M. Malinová ◽  
B. Koubková ◽  
J. Száková ◽  
V. Zídek ◽  
...  
Keyword(s):  
Contaminated Soils ◽  
Female Rats ◽  
Male Rats ◽  
Copper Level ◽  
Experimental Diet ◽  
Male And Female ◽  
Risk Elements ◽  
Element Contents ◽  
Risk Element

The long-term accumulation of risk elements (As, Cd, Pb) originated from differently contaminated soils in rat organism was investigated during a model two-generation experiment. The effect of soil contamination level, gender, and length of exposure as well as the interactions between risk elements and selected essential macro- and microelements were studied. Rat diet contained 10% of individual soils (based on dry weight): (i) Fluvisol heavily polluted by As, Cd, Zn, and Pb, (ii) Luvisol contaminated by As, Cd, and Zn, and (iii) uncontaminated Chernozem. Male and female Wistar rats used for the experiment were housed in cages in a room with controlled temperature for 60 days and were fed ad libitum the mentioned diets. Subsequently, the pregnant females were continuously fed the experimental diet until weaning when the young animals were separated to male and female and fed the experimental diet till day 110 of age. The element contents in rat tissues reflected the risk element contents in contaminated soils. The bioaccessibility and bioavailability of the risk elements decreased in the order Cd>As>Pb and was affected by the soil physicochemical parameters. No significant differences were observed between male and female rats as well as between the first and the second generation. However, interactions were reported among the risk elements where the high cadmium content in Fluvisol resulted in increasing arsenic accumulation in the rat liver. Moreover, arsenic–copper interactions were observed where significant increase of the copper level was determined in kidney of the animals fed Luvisol exceeding 50-fold the maximum permissible limits for As content in agricultural soils. Among the hematological and biochemical characteristics of rats, total erythrocyte count (Er), hematocrit (Hct) increased confirming adverse effect of soil-derived risk elements especially in male rats.  

scholarly journals Facilitation of the HPA Axis to a Novel Acute Stress Following Chronic Stress Exposure Modulates Histone Acetylation and the ERK/MAPK Pathway in the Dentate Gyrus of Male Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2942-2952 ◽  
Author(s):  
Chantelle L. Ferland ◽  
Erin P. Harris ◽  
Mai Lam ◽  
Laura A. Schrader
Keyword(s):  
Dentate Gyrus ◽  
Histone Acetylation ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Acute Stress ◽  
Male Rats ◽  
Stress Exposure ◽  
Erk Activation ◽  
Acute And Chronic Stress ◽  
Acute Stressor

Evidence suggests that when presented with novel acute stress, animals previously exposed to chronic homotypic or heterotypic stressors exhibit normal or enhanced hypothalamic-pituitary-adrenal (HPA) response compared with animals exposed solely to that acute stressor. The molecular mechanisms involved in this effect remain unknown. The extracellular signal-regulated kinase (ERK) is one of the key pathways regulated in the hippocampus in both acute and chronic stress. The aim of this study was to examine the interaction of prior chronic stress, using the chronic variable stress model (CVS), with exposure to a novel acute stressor (2,5-dihydro-2,4,5-trimethyl thiazoline; TMT) on ERK activation, expression of the downstream protein BCL-2, and the glucocorticoid receptor co-chaperone BAG-1 in control and chronically stressed male rats. TMT exposure after chronic stress resulted in a significant interaction of chronic and acute stress in all 3 hippocampus subregions on ERK activation and BCL-2 expression. Significantly, acute stress increased ERK activation, BCL-2 and BAG-1 protein expression in the dentate gyrus (DG) of CVS-treated rats compared with control, CVS-treated alone, and TMT-only animals. Furthermore, CVS significantly increased ERK activation in medial prefrontal cortex, but acute stress had no significant effect. Inhibition of corticosterone synthesis with metyrapone had no significant effect on ERK activation in the hippocampus; therefore, glucocorticoids alone do not mediate the molecular effects. Finally, because post-translational modifications of histones are believed to play an important role in the stress response, we examined changes in histone acetylation. We found that, in general, chronic stress decreased K12H4 acetylation, whereas acute stress increased acetylation. These results indicate a molecular mechanism by which chronic stress-induced HPA axis plasticity can lead to neurochemical alterations in the hippocampus that influence reactivity to subsequent stress exposure. This may represent an important site of dysfunction that contributes to stress-induced pathology such as depression, anxiety disorders, and posttraumatic stress disorder.

scholarly journals Local Cerebral Glucose Utilization in Normal Female Rats: Variations during the Estrous Cycle and Comparison with Males

1985 ◽  
Vol 5 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Alison M. Crane ◽  
Louis Sokoloff
Keyword(s):  
Estrous Cycle ◽  
Glucose Utilization ◽  
Brain Regions ◽  
Female Rats ◽  
Male Rats ◽  
Normal Male ◽  
Normal Female ◽  
Female Rat ◽  
Males And Females ◽  
The Brain

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.

scholarly journals A New Spontaneously Diabetic Non-obese Torii Rat Strain With Severe Ocular Complications

2000 ◽  
Vol 1 (2) ◽  
pp. 89-100 ◽  
Author(s):  
Masami Shinohara ◽  
Taku Masuyama ◽  
Toshiyuki Shoda ◽  
Tadakazu Takahashi ◽  
Yoshiaki Katsuda ◽  
...  
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Ocular Complications ◽  
Tractional Retinal Detachment ◽  
Term Survival ◽  
Disease Condition ◽  
Rat Strain

A new spontaneously diabetic strain of the Sprague-Dawley rat was established in 1997 and named the SDT (Spontaneously Diabetic Torii) rat. In this research, we investigated the characteristics of the disease condition in the SDT rats. The time of onset of glucosuria was different between male and female SDT rats; glucosuria appeared at approximately 20 weeks of age in male rats and at approximately 45 weeks of age in female rats. A cumulative incidence of diabetes of 100% was noted by 40 weeks of age in male rats, while it was only 33.3% even by 65 weeks of age in female rats. The survival rate up to 65 weeks of age was 92.9% in male rats and 97.4% in female rats. Glucose intolerance was observed in male rats from 16 weeks of age. The clinical characteristics of the male SDT rats were (1) hyperglycemia and hypoinsulinemia (from 25 weeks of age); (2) long-term survival without insulin treatment; (3) hypertriglyceridemia (by 35 weeks of age); however, no obesity was noted in any of the male rats. The histopathological characteristics of the male rats with diabetes mellitus (DM) were (1) fibrosis of the pancreatic islets (by 25 weeks of age); (2) cataract (by 40 weeks of age); (3) tractional retinal detachment with fibrous proliferation (by 70 weeks of age) and (4) massive hemorrhaging in the anterior chamber (by 77 weeks of age). These clinical and histopathological characteristics of the disease in SDT rats resemble those of human Type 2 diabetes with insulin hyposecretion. In conclusion, SDT rat is considered to be a potentially useful model for studies of diabetic retinopathy encountered in humans.

Maternal stress does not exacerbate long-term bone deficits in female rats born growth restricted, with differential effects on offspring bone health

2018 ◽  
Vol 314 (2) ◽  
pp. R161-R170 ◽  
Author(s):  
Kristina Anevska ◽  
Jean N. Cheong ◽  
John D. Wark ◽  
Mary E. Wlodek ◽  
Tania Romano
Keyword(s):  
Bone Health ◽  
Bending Strength ◽  
Maternal Stress ◽  
Quantitative Computed Tomography ◽  
Peripheral Quantitative Computed Tomography ◽  
Female Offspring ◽  
Female Rats ◽  
Stress Exposure ◽  
Wistar Kyoto

Females born growth restricted have poor adult bone health. Stress exposure during pregnancy increases risk of pregnancy complications. We determined whether maternal stress exposure in growth-restricted females exacerbates long-term maternal and offspring bone phenotypes. On gestational day 18, bilateral uterine vessel ligation (restricted) or sham (control) surgery was performed on Wistar-Kyoto rats. At 4 mo, control and restricted females were mated and allocated to unstressed or stressed pregnancies. Stressed pregnancies had physiological measurements performed; unstressed females were not handled. After birth, mothers were aged to 13 mo. Second-generation (F2) offspring generated four experimental groups: control unstressed, restricted unstressed, control stressed and restricted stressed. F2 offspring were studied at postnatal day 35 (PN35), 6, 12, and 16 mo. Peripheral quantitative computed tomography was performed on maternal and F2 offspring femurs. Restricted females, irrespective of stress during pregnancy, had decreased endosteal circumference, bending strength, and increased osteocalcin concentrations after pregnancy at 13 mo. F2 offspring of stressed mothers were born lighter. F2 male offspring from stressed pregnancies had decreased trabecular content at 6 mo and decreased endosteal circumference at 16 mo. F2 female offspring from growth-restricted mothers had reduced cortical thickness at PN35 and reduced endosteal circumference at 6 mo. At 12 mo, females from unstressed restricted and stressed control mothers had decreased trabecular content. Low birth weight females had long-term bone changes, highlighting programming effects on bone health. Stress during pregnancy did not exacerbate these programmed effects. Male and female offspring responded differently to maternal growth restriction and stress, indicating gender-specific programming effects.

scholarly journals Chronic Stress and Gonadectomy Affect the Expression of Cx37, Cx40 and Cx43 in the Spinal Cord

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1330
Author(s):  
Marija Jurić ◽  
Marta Balog ◽  
Vedrana Ivić ◽  
Benjamin Benzon ◽  
Anita Racetin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Chronic Stress ◽  
Pain Perception ◽  
Female Rats ◽  
Male Rats ◽  
Stress Exposure ◽  
Cx43 Expression ◽  
Stressed Group ◽  
Transmission Electron ◽  
Chronic Pain Conditions

The study aimed to determine whether the exposure to chronic stress and/or performance of gonadectomy might lead to disturbance in the expression of connexin (Cx) 37, 40 and 43 in the spinal cord (SC), as a potential explanation for sex differences in stress-related chronic pain conditions. After the rats were sham-operated or gonadectomized, three 10-day sessions of sham or chronic stress were applied. Immunohistochemistry and transmission electron microscopy (TEM) were used to examine Cx localization and expression in the SC. The gonadectomy resulted in an increase of Cx37 expression in the dorsal horn (DH) of the female rats, but chronic stress suppressed the effects of castration. In male rats, only the combined effects of castration and chronic stress increased Cx37 expression. The influence of chronic stress on the DH Cx40 expression was inversely evident after the castration: increased in the ovariectomized female rats, while decreased in the orchidectomized male rats. We did not find any effect of chronic stress and castration, alone or together, on Cx43 expression in the DH, but the percentage of Cx43 overlapping the astrocyte marker glial fibrillary acidic protein (gfap) increased in the male stressed group after the castration. In conclusion, the association of the chronic stress with sex hormone depletion results in disturbances of the SC Cx expression and might be a possible mechanism of disturbed pain perception after chronic stress exposure.

scholarly journals Adolescent Stress Increases Adult Ethanol Self-administration and Alters Ventral Tegmental Area GABA Signaling

2019 ◽  
Author(s):  
David A Connor ◽  
Ruthie E Wittenberg ◽  
Jillian Drogin ◽  
Allison Mak ◽  
John A Dani
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Alcohol Use Disorders ◽  
Early Life Stress ◽  
Male Rats ◽  
Stress Exposure ◽  
Self Administration ◽  
Adolescent Stress ◽  
Gaba Signaling

AbstractAlcohol use disorders (AUDs) continue to be a significant public health problem. Early life stress and adversity have long-lasting effects on a wide range of behaviors, including responses to drugs of abuse. Epidemiological evidence indicates that exposure to early life stress contributes to alcohol use disorders and, while it is known that stress and alcohol both act on overlapping mesolimbic circuitry, the cellular mechanisms underlying the relationship between stress and alcohol intake are not well understood. Previous work has demonstrated that acute stress increases ethanol intake mediated by changes in GABA signaling within the ventral tegmental area (VTA). Here we investigated if adolescent stress exposure might elicit long-term, persistent increases in ethanol self-administration associated with altered VTA GABA signaling. To this end, we exposed adolescent postnatal day (PND) 28 male rats to 14 days of chronic variable stress (CVS) and then examined operant ethanol self-administration begun at least 30 days later. We found that adolescent stress exposure resulted in significantly increased ethanol self-administration in adulthood. In contrast, adult (PND 82) male rats exposed to the same CVS protocol did not display increased ethanol self-administration that was begun 30 days later. Furthermore, we found that adolescent stress exposure resulted in enhancement of ethanol-induced GABA signaling onto VTA dopamine neurons and impairments in VTA GABA chloride homeostasis. The results indicate that adolescence is a period vulnerable to stress, which produces long-term changes in VTA GABA signaling associated with increased ethanol self-administration behavior.

scholarly journals Dynamic Alterations of miR-34c Expression in the Hypothalamus of Male Rats after Early Adolescent Traumatic Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Chuting Li ◽  
Yuan Liu ◽  
Dexiang Liu ◽  
Hong Jiang ◽  
Fang Pan
Keyword(s):  
Traumatic Stress ◽  
Memory Impairment ◽  
Term Effect ◽  
Male Rats ◽  
Early Adolescent ◽  
Short Term ◽  
Corticotrophin Releasing Factor ◽  
Long Term Effect ◽  
The Brain

Several types of microRNA (miRNA) overexpression in the brain are associated with stress. One of the targets of miR-34c is the stress-related corticotrophin releasing factor receptor 1 mRNA (CRFR1 mRNA). Here we will probe into the short-term effect and long-term effect of early adolescent traumatic stress on the expression of miR-34c and CRFR1 mRNA. Traumatic stress was established by electric foot shock for six consecutive days using 28-day rats. The anxiety-like behaviors, memory damage, CRFR1 protein, CRFR1 mRNA, and miR-34c expression were detected in our study. The results of our study proved that exposure to acute traumatic stress in early adolescent can cause permanent changes in neural network, resulting in dysregulation of CRFR1 expression and CRFR1 mRNA and miR-34c expression in hypothalamus, anxiety-like behavior, and memory impairment, suggesting that the miR-34c expression in hypothalamus may be an important factor involved in susceptibility to PTSD.

Neuropharmacological analysis of the control of LH secretion in gonadectomized male and female rats: altered hypothalamic responses to inhibitory neurotransmitters in long-term castrated rats

1988 ◽  
Vol 119 (1) ◽  
pp. 15-21 ◽  
Author(s):  
O. F. X. Almeida ◽  
K. E. Nikolarakis ◽  
A. Herz
Keyword(s):  
Opioid Receptor ◽  
Female Rats ◽  
Male Rats ◽  
Dopaminergic Agonists ◽  
Male And Female ◽  
Opioid Agonists ◽  
Male And Female Rats ◽  
Lh Release ◽  
Lh Secretion

ABSTRACT The control of LHRH and LH by neurotransmitters and neuromodulators such as the endogenous opioid peptides is essentially the same in intact adult male and female rats: adrenergic and dopaminergic agonists stimulate LH release and opioid agonists inhibit it. Several weeks after gonadectomy, however, the contribution of the endogenous ligands of adrenergic, dopaminergic and opioidergic receptors to the control of LHRH is altered. A detailed pharmacological analysis in long-term ovariectomized females confirmed previous reports that adrenergic and dopaminergic agonists still enhance secretion of LHRH and LH and opioid receptor agonists still suppress it. A similar investigation in long-term castrated males also confirmed previous reports that opioid agonists fail to block LH secretion. In addition, we have found that while adrenergic and dopaminergic agonists cause increases in serum concentrations of LH, adrenoreceptor and dopamine receptor antagonists do not inhibit LH release in long-term castrates. Furthermore, the opioid antagonist naloxone does not raise serum LH levels in either sex after long-term gonadectomy. These observations therefore imply reduced opioidergic, dopaminergic and adrenergic transmission, in relation to LHRH release, after longterm castration. In addition, opioid receptor activity (assessed by responsiveness to an opioid receptor agonist) of female rats is maintained, whereas that of male rats is lost, after long-term gonadectomy. J. Endocr. (1988) 119, 15–21

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