LPS reduces BDNF and VEGF expression in the structures of the HPA axis of chronic social stressed female rats

Abstract Prolonged exposure to environmental stress activates the hypothalamic-pituitary-adrenal (HPA) axis and generally disrupts the hypothalamic-pituitary-gonadal axis. Because CRF expression in the central nucleus of the amygdala (CeA) is a key modulator in adaptation to chronic stress, and central administration of CRF inhibits the hypothalamic GnRH pulse generator, we tested the hypothesis that overexpression of CRF in the CeA of female rats alters anxiety behavior, dysregulates the HPA axis response to stress, changes pubertal timing, and disrupts reproduction. We used a lentiviral vector to increase CRF expression site specifically in the CeA of preweaning (postnatal day 12) female rats. Overexpression of CRF in the CeA increased anxiety-like behavior in peripubertal rats shown by a reduction in time spent in the open arms of the elevated plus maze and a decrease in social interaction. Paradoxically, puberty onset was advanced but followed by irregular estrous cyclicity and an absence of spontaneous preovulatory LH surges associated with proestrous vaginal cytology in rats overexpressing CRF. Despite the absence of change in basal corticosterone secretion or induced by stress (lipopolysaccharide or restraint), overexpression of CRF in the CeA significantly decreased lipopolysaccharide, but not restraint, stress-induced suppression of pulsatile LH secretion in postpubertal ovariectomized rats, indicating a differential stress responsivity of the GnRH pulse generator to immunological stress and a potential adaptation of the HPA axis to chronic activation of amygdaloid CRF. These data suggest that the expression profile of this key limbic brain CRF system might contribute to the complex neural mechanisms underlying the increasing incidence of early onset of puberty on the one hand and infertility on the other attributed to chronic stress in modern human society.

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Hormonal and Behavioral Characteristics of Prenatally Stressed Female Rats in an Experimental Model of Depression

Neuroscience and Behavioral Physiology ◽

10.1007/s11055-019-00772-6 ◽

2019 ◽

Vol 49 (5) ◽

pp. 573-579

Author(s):

N. E. Ordyan ◽

S. G. Pivina ◽

V. I. Mironova ◽

V. K. Akulova ◽

V. V. Rakitskaya

Keyword(s):

Experimental Model ◽

Female Rats ◽

Behavioral Characteristics ◽

Stressed Female ◽

Prenatally Stressed

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N-3 Polyunsaturated Fatty Acid Improved Depression via Neuroendocrine and Serotonergic System in Post-Menopausal Rats with Maternal Separation and Chronic Mild Stress

Current Developments in Nutrition ◽

10.1093/cdn/nzaa057_015 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1199-1199

Author(s):

Jeong-Eun Choi ◽

Yongsoon Park

Keyword(s):

Hpa Axis ◽

Maternal Separation ◽

Chronic Mild Stress ◽

Female Rats ◽

Serotonin Level ◽

Mild Stress ◽

Total N ◽

Serotonergic Pathway ◽

Post Menopausal ◽

Hpa Axis Activity

Abstract Objectives The purpose of the present study was to investigate the hypothesis that lifetime n-3 polyunsaturated fatty acids (PUFA) intake improved depression through serotonergic pathway in post-menopausal rats with chronic mild stress (CMS) and maternal separation (MS). Methods Female rats were fed diets with 0% or 1 energy % n-3 PUFA during lifetime from embryonic day (ED) 0 to postnatal day (PND) 112, or 1% n-3 PUFA before weaning (ED 0-PND 20), or after weaning (PND 20–112). The rats in four diet group were allocated to brief separation from dam (non-MS group) or long-term separation (MS group) on PND 2–14, and then underwent CMS on PND 91–105 after ovariectomy. Thus, there were eight groups in total (n = 8/group). Results MS + CMS increased depressive behaviors, and modified hypothalamic-pituitary-adrenal (HPA) axis activity, inflammation, serotonergic and glutamatergic neurotransmission, and related miRNAs as compared to CMS alone. N-3 PUFA decreased depressive behaviors by decreasing immobility while increasing swimming during forced swim test, and increasing sucrose preference in rats with MS + CMS and with CMS. N-3 PUFA decreased HPA axis activity by modifying expressions of corticotrophin releasing factor and glucocorticoid receptor, and levels of adrenocorticotropic hormone and corticosterone. N-3 PUFA also reduced levels of TNF-α, IL-1β, IL-6, PGE2, and miRNA-218, and increased serotonergic neurotransmission, including expressions of cAMP response element binding protein, brain-derived neurotrophic factor and serotonin 1A receptor, and serotonin level, and expression of miRNA-155. In addition, lifetime supplementation of n-3 PUFA had greater effect than pre- or post-supplementation. N-3 PUFA had no effect on glutamatergic pathway including α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor and N-methyl-D-aspartate receptor. Conclusions The present study suggested that lifetime n-3 PUFA improved depression in post-menopausal rats with MS + CMS through modulation of serotonergic pathway by decreasing HPA axis activity but not glutamatergic pathway. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1A2B6002486).

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Neuroendocrine disruption is associated to infertility in chronically stressed female rats

Reproductive Biology ◽

10.1016/j.repbio.2020.07.011 ◽

2020 ◽

Vol 20 (4) ◽

pp. 474-483

Author(s):

Socorro Retana-Márquez ◽

Lizbeth Juárez-Rojas ◽

Alejandra Ávila-Quintero ◽

Susana Rojas-Maya ◽

Gerardo Perera ◽

...

Keyword(s):

Female Rats ◽

Stressed Female

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Pharmacological evidence for β2-adrenoceptor in right atria from stressed female rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y99-031 ◽

1999 ◽

Vol 77 (6) ◽

pp. 432-440 ◽

Cited By ~ 13

Author(s):

R C Spadari-Bratfisch ◽

I N Santos ◽

LCM Vanderlei ◽

F K Marcondes

Keyword(s):

Estrous Cycle ◽

Model Equation ◽

Female Rats ◽

Cycle Phase ◽

Response Curves ◽

Chronotropic Response ◽

Site Model ◽

Stressed Female ◽

Right Atria ◽

Shock Stress

The purpose of the present study was to demonstrate a physiological response to TA2005, a potent β2-adrenoceptor (β2-AR) selective agonist, in right atria isolated from stressed female rats under the influence of the estrous cycle. We obtained concentration-response curves to the agonist in the presence and in the absence of selective antagonists in right atria isolated from female rats submitted to three daily foot-shock sessions (30 min duration, 120 pulses of 1.0 mA, 1.0 s, applied at random intervals of 5-25 s) and sacrificed at estrus or diestrus. Our results showed that the pD2 values of TA2005 were not influenced by estrous cycle phase or foot-shock stress. However, in right atria from stressed rats sacrificed during diestrus, the concentration-response curve to TA2005 was biphasic, with a response being obtained at concentrations of 0.1 nM, whereas during estrus no response was observed at doses lower than 3 nM. ICI118,551, a β2-AR antagonist, abolished the response to nanomolar concentrations of TA2005 in right atria from stressed rats at diestrus, with no changes in agonist pD2 values in right atria from control rats (7.47 ± 0.09, p > 0.05) but a 3-fold decrease in pD2 values of TA2005 in right atria from foot shock stressed rats (7.90 ± 0.07, p [Formula: see text] 0.05). Concentration-response curves to TA2005 in the presence of ICI118,551 were best fitted by a one-site model equation. The β1-AR antagonist, CGP20712A, shifted to the right only the second part of the concentration-response curves to the agonist, unmasking the putative β2-AR-mediated response to the agonist in tissues isolated from stressed rats at diestrus. Under this condition, concentration-response curves to the agonist were best fitted by a two-site model equation. pD2 and maximum response of TA2005 interaction with β1- and putative β2-adrenoceptor components were calculated. Schild analyses gave a pKB value for CGP20712A that was typical for the interaction with β1-AR in each experimental group. pKB values for ICI118,551 could not be obtained in stressed rats sacrificed at diestrus since Schild plot slopes were lower than 1.0. In right atria from control rats, ICI118,551 pKB values were similar to reported values for the interaction of the antagonist with β1-AR. These results confirm that a heterogenous β-AR population mediating the chronotropic response to catecholamines can be demonstrated in right atria from foot shock stressed female rats sacrificed at diestrus. The stress-induced response seems to be mediated by the β2-AR subtype. Right atria from rats sacrificed during estrus are protected against stress-induced alterations on the homogeneity of β-AR population.Key words: foot-shock stress, TA2005, ICI118,551, CGP20712A, estrus, diestrus.

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