Abstract 17: Early Life Stress Sensitizes The Angiotensin II-elicited Hypertensive Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Baojian Xue ◽  
Terry Beltz ◽  
Fang Guo ◽  
David M Pollock ◽  
Jennifer S Pollock ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Proinflammatory Cytokines ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Male Rats ◽  
Sprague Dawley ◽  
Cns Inflammation ◽  
Wide Range ◽  
The Brain

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.

Abstract 403: Renal Denervation Reveals Renal Sympathetic Activation in Adult Rats Exposed to Early Life Stress

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Analia S Loria ◽  
Michael W Brands ◽  
David M Pollock ◽  
Jennifer S Pollock
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Renal Denervation ◽  
Early Life Stress ◽  
Male Rats ◽  
Renal Nerves ◽  
Adult Rats ◽  
Baseline Conditions ◽  
Control Sham ◽  
Renal Sympathetic

We previously reported that maternal separation (MS), a model of early life stress, does not modify baseline blood pressure in adult rats, but increases sensitivity to hypertensive stimuli. Under baseline conditions, adult male rats exposed to MS have significantly reduced glomerular filtration rate (GFR). Acute phenylephrine-induced reductions in renal blood flow is significantly attenuated in rats exposed to MS compared to control rats. Furthermore, norephinephrine (NE) content was increased in renal cortex of MS rats compared to control rats (p<0.05). These data indicate that MS induces increased renal sympathetic outflow. Thus, we hypothesized that renal denervation will normalize GFR in rats exposed to MS. Male WKY rat pups were separated from their mothers for 3 hrs/day during the morning hours from day 2 to 14 of life. Male non-separated littermates served as control rats. Experiments were performed in 300-320 g adult rats. Denervation (DnX) was performed mechanically stripping all visible renal nerves followed by topical phenol (10%) on the renal artery. Control-sham, MS-sham, control-DnX, and MS-DnX rats were instrumented with catheters in the femoral vein and abdominal aorta. Rats were placed in metabolic cages, connected to swivels, and allowed to recover for 4-5 days. Sodium intake was clamped at 2.8 mEq/day in both groups by combining sodium deficient diet and 24 hr/day 0.9% iv saline infusion (20 ml/day). GFR was determined by plasma clearance of [125I]iothalamate in the conscious state. During baseline conditions, MAP was not different between control-sham and MS-sham rats (99±4 vs 97±2 mmHg, respectively). MAP was reduced in both control-DnX and MS-DnX rats (91±2 mmHg and 83±3 mmHg, p<0.05, respectively) compared with the respective sham group. The reduction in MAP tended to be greater in MS than in control rats (-9±1 and -14±2 mmHg, p=0.074). DnX did not modify GFR in control rats (sham: 3.1±0.1 ml/min vs DnX: 3.5±0.4 ml/min). However, DnX significantly increased GFR in rats exposed to MS (sham: 2.4±0.2 ml/min vs DnX: 3.8±0.4 ml/min, p<0.05). These data support our hypothesis that MS induces increased renal sympathetic tone to reduce GFR in MS male rats, and may contribute to the exacerbated response to hypertensive stimuli observed in MS rats.

IMPACT OF EARLY LIFE STRESS ON ANTI-DEPRESSANT SENSITIVITY

2021 ◽  
pp. 123-132
Author(s):  
V.A. Vokina
Keyword(s):  
Open Field ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Anxiety Level ◽  
Male Rats ◽  
Porsolt Test ◽  
The Impact ◽  
Sexually Mature

Long-term consequences of impaired perinatal development are very significant. They appear during the neonatal period and in the first years of life, and persist during ontogenesis. There is little data on the impact of any prenatal factors on the sensitivity of a sexually mature organism to medications. The aim of the study is to assess the impact of early life stress on the development of individual antidepressant sensitivity. Materials and Methods. The authors conducted the experiments on sexually mature outbred male rats. To simulate the early life stress, a standard protocol was used. From the 2nd to 15th days of the postnatal period the pup rats were separated from their mother for 3 hours and kept in an incubator. The open-field test, Porsolt test and Sucrose consumption test were used to determine rat’s anxiety level as well as motor, orientation and exploratory activity at puberty. Then, for 14 days, the rats were intragastrically administered with a fluoxetine solution (10 mg/kg/daily), followed by their full examination. Statistical analysis of results was performed using the Mann-Whitney U-test to compare unrelated groups and Wilcoxon's test to compare related groups. Results. Fluoxetine did not have a pronounced antidepressant effect in animals that survived the early life stress. Such animals demonstrated passive floating during the Porsolt test, without any changes in immobility time. When testing in an open field, a sharp increase in the number of freezing behavior was observed, which was an indicator of an increased anxiety level in animals. Conclusion. The results obtained indicate that the long-term effects of neonatal stress may be associated with a change in antidepressant sensitivity or an increase in development of unwanted adverse reactions. Keywords: early life stress, depression, antidepressants, fluoxetine, rats. Отдаленные последствия нарушения перинатального развития весьма значительны и не только проявляются в период новорожденности и в первые годы жизни, но и сохраняются в период онтогенеза. Данные о влиянии каких-либо пренатальных факторов на чувствительность половозрелого организма к действию лекарственных веществ в доступной литературе представлены незначительно. Цель исследования – оценить роль стресса раннего периода жизни в формировании индивидуальной чувствительности к действию антидепрессантов. Материалы и методы. Эксперименты проведены на половозрелых беспородных крысах-самцах. Для моделирования стресса раннего периода жизни использовали стандартный протокол, подразумевающий отделение детенышей от матери со 2-го по 15-й дни постнатального периода на 3 ч в условиях инкубатора. В половозрелом возрасте проводили оценку уровня тревожности, двигательной и ориентировочно-исследовательской активности крыс в условиях теста открытого поля, теста Порсолта и теста «Потребление раствора сахарозы». Затем в течение 14 дней крысам внутрижелудочно вводили раствор флуоксетина (10 мг/кг/сут), после чего обследование повторяли в том же объеме. Статистический анализ результатов исследования проводили с использованием U-критерия Манна–Уитни для сравнения несвязанных групп и критерия Вилкоксона для сравнения связанных групп. Результаты. У животных, переживших стресс раннего периода жизни, флуоксетин не оказывал выраженного антидепрессантного действия. У данных животных в тесте Порсолта преобладало пассивное плавание, без изменения длительности иммобильности. При тестировании в открытом поле наблюдалось резкое повышение числа актов фризинга, что является показателем повышенного уровня тревожности у животных. Выводы. Полученные результаты свидетельствуют о том, что отдаленные последствия неонатального стресса могут быть связанны с изменением чувствительности к действию антидепрессантов или повышением риска развития нежелательных побочных реакций. Ключевые слова: стресс раннего периода жизни, депрессия, антидепрессанты, флуоксетин, крысы.

Long-term effects of early life stress on the brain monoamines level in the rats

2013 ◽  
Vol 43 (1) ◽  
pp. 79
Author(s):  
R. Ghalamghash ◽  
H.Z. Mammedov ◽  
H. Ashayeri ◽  
A. Hosseini
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Long Term Effects ◽  
Brain Monoamines ◽  
The Brain

scholarly journals Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

2020 ◽  
Vol 21 (19) ◽  
pp. 7212
Author(s):  
Mayumi Nishi
Keyword(s):  
Child Abuse ◽  
Hpa Axis ◽  
Brain Function ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Emotional Behavior ◽  
Neural Basis ◽  
The Brain

Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.

The adaptive and maladaptive continuum of stress responses – a hippocampal perspective

2015 ◽  
Vol 26 (4) ◽  
Author(s):  
Deepika Suri ◽  
Vidita A. Vaidya
Keyword(s):  
Stress Responses ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Negative Consequences ◽  
Functional Responses ◽  
Physiological Level ◽  
Early Stress ◽  
Wide Range ◽  
Potential Factors

AbstractExposure to stressors elicits a spectrum of responses that span from potentially adaptive to maladaptive consequences at the structural, cellular and physiological level. These responses are particularly pronounced in the hippocampus where they also appear to influence hippocampal-dependent cognitive function and emotionality. The factors that influence the nature of stress-evoked consequences include the chronicity, severity, predictability and controllability of the stressors. In addition to adult-onset stress, early life stress also elicits a wide range of structural and functional responses, which often exhibit life-long persistence. However, the outcome of early stress exposure is often contingent on the environment experienced in adulthood, and could either aid in stress coping or could serve to enhance susceptibility to the negative consequences of adult stress. This review comprehensively examines the consequences of adult and early life stressors on the hippocampus, with a focus on their effects on neurogenesis, neuronal survival, structural and synaptic plasticity and hippocampal-dependent behaviors. Further, we discuss potential factors that may tip stress-evoked consequences from being potentially adaptive to largely maladaptive.

scholarly journals Lasting Differential Effects on Plasticity Induced by Prenatal Stress in Dorsal and Ventral Hippocampus

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Gayane Grigoryan ◽  
Menahem Segal
Keyword(s):  
Prenatal Stress ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Brain Structures ◽  
Traumatic Experience ◽  
Stressful Stimulation ◽  
The Brain ◽  
Two Sectors ◽  
Structure And Functions

Early life adversaries have a profound impact on the developing brain structure and functions that persist long after the original traumatic experience has vanished. One of the extensively studied brain structures in relation to early life stress has been the hippocampus because of its unique association with cognitive processes of the brain. While the entire hippocampus shares the same intrinsic organization, it assumes different functions in its dorsal and ventral sectors (DH and VH, resp.), based on different connectivity with other brain structures. In the present review, we summarize the differences between DH and VH and discuss functional and structural effects of prenatal stress in the two sectors, with the realization that much is yet to be explored in understanding the opposite reactivity of the DH and VH to stressful stimulation.

scholarly journals microRNAs as novel antidepressant targets: converging effects of ketamine and electroconvulsive shock therapy in the rat hippocampus

2013 ◽  
Vol 16 (8) ◽  
pp. 1885-1892 ◽  
Author(s):  
Richard M. O'Connor ◽  
Susan Grenham ◽  
Timothy G. Dinan ◽  
John F. Cryan
Keyword(s):  
Electroconvulsive Shock ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Shock Therapy ◽  
Contributory Factor ◽  
Sprague Dawley ◽  
Antidepressant Treatments ◽  
Sprague Dawley Rats ◽  
Antidepressant Action

Abstract Early-life stress is a main contributory factor to the onset of depression. Treatments remain inadequate and as such, a large unmet medical need for novel therapeutics remains. Impeding advancement is the poor understanding of the molecular pathology. microRNAs (miRNAs) are novel regulators of gene expression. A paucity of information regarding their role in depressive pathology and antidepressant action remains. This study investigated changes to hippocampal miRNA levels induced via early-life stress in Sprague–Dawley rats and whether antidepressant treatments could reverse these changes. Investigated were the selective serotonin reuptake inhibitor fluoxetine, the rapid acting N-methyl-d-aspartate receptor antagonist ketamine and electroconvulsive shock therapy (ECT). Microarray analysis revealed early-life stress affected the expression of multiple hippocampal miRNAs. Antidepressant treatments reversed some of these effects including a stress-induced change to miR-451. Ketamine and ECT possessed the highest number of common targets suggesting convergence on common pathways. Interestingly all three treatments possessed miR-598-5p as a common target. This demonstrates that changes to hippocampal miRNA expression may represent an important component of stress-induced pathology and antidepressant action may reverse these.

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