PI3K/Akt/NF-κB signaling pathway regulates behaviors in adolescent female rats following with neonatal maternal deprivation and chronic mild stress

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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Effects of Chronic Mild Stress on the Development of Atherosclerosis and Expression of Toll-Like Receptor 4 Signaling Pathway in Adolescent Apolipoprotein E Knockout Mice

Journal of Biomedicine and Biotechnology ◽

10.1155/2009/613879 ◽

2009 ◽

Vol 2009 ◽

pp. 1-13 ◽

Cited By ~ 16

Author(s):

Hongfeng Gu ◽

Chaoke Tang ◽

Kuang Peng ◽

Hui Sun ◽

Yongzong Yang

Keyword(s):

Apolipoprotein E ◽

Signaling Pathway ◽

Knockout Mice ◽

Chronic Mild Stress ◽

Mild Stress ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Apolipoprotein E Knockout Mice ◽

Tlr4 Signaling Pathway ◽

Myeloid Differentiation Factor

Here, we investigated the effect of chronic mild stress (CMS) on the development of atherosclerosis as well as the expression of Toll-like receptors (TLRs) signaling pathway in adolescent apolipoprotein E knockout (apoE-/-) mice. Mice were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein E knockout mice subjected to CMS, we compared gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87 genes. We found that atherosclerosis lesions both in aortic tress and sinuses of CMS mice were significantly increased linearly in response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88 (MyD88), and IL-1β, and 28 genes were downregulated compared with nonstressed mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were associated with significant increases in levels of expression of TLR4, MyD88, nuclear factorκB (NF-κB), MCP-1, IL-1β, TNF-α, and sICAM-1. Taken together, our results suggest an important role for TLR4 signaling pathway in atherosclerosis in a CMS mouse model.

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Combination of chronic mild stress and forced swim test in male and female rats: Behavioral and neurochemical effects

European Neuropsychopharmacology ◽

10.1016/s0924-977x(02)80317-0 ◽

2002 ◽

Vol 12 ◽

pp. 249 ◽

Cited By ~ 1

Author(s):

C. Dalla ◽

M. Xagoraris ◽

S. Daskas ◽

K. Antoniou ◽

A. Sfikakis ◽

...

Keyword(s):

Forced Swim Test ◽

Chronic Mild Stress ◽

Female Rats ◽

Mild Stress ◽

Male And Female ◽

Swim Test ◽

Forced Swim ◽

Male And Female Rats

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Role of purinergic signaling pathways in the adaptogenic-like activity of methyl jasmonate in rats exposed to unpredictable chronic mild stress

Drug Metabolism and Personalized Therapy ◽

10.1515/dmdi-2020-0117 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Oritoke M. Aluko ◽

Solomon Umukoro

Keyword(s):

Methyl Jasmonate ◽

Adenosine Deaminase ◽

Signaling Pathway ◽

Purinergic Signaling ◽

Hematological Parameters ◽

Chronic Mild Stress ◽

Mild Stress ◽

Unpredictable Chronic Mild Stress ◽

Swimming Endurance

AbstractObjectivesPurinergic signaling pathway has been implicated in maladaptation of animals subjected to chronic stress. Previous studies have shown that methyl jasmonate (MJ) exhibited adaptogenic properties in mice exposed to unpredictable chronic mild stress (UCMS) via antioxidant and neuroprotective-related mechanisms.MethodsThis study evaluated the role of purinergic system in adaptogenic-like activity of MJ. Male Wistar rats were treated intraperitoneally with vehicle (10 mL/kg) or MJ (25, 50, or 100 mg/kg) 30 min prior exposure to UCMS. Thereafter, rats were assessed for swimming endurance in forced swim test (FST) and post-swimming motor coordination on beam walk test (BWT) apparatus. The rats’ brains were processed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine deaminase, and arginase quantification. Hematological parameters, cholesterol, triglyceride, creatinine, and urea nitrogen were also determined.ResultsMJ prolonged swimming endurance time and reversed stress-induced post-swimming motor dysfunction. The altered hematological parameters induced by UCMS in rats were significantly (p<0.05) attenuated by MJ. MJ also reversed UCMS-induced alterations of total cholesterol, triglyceride, creatinine, and urea nitrogen levels. MJ averted UCMS-induced alterations in purinergic system by decreasing ATP and ADP hydrolysis, adenosine deaminase, and arginase activities in rats’ brains.ConclusionsOverall, these findings further suggest that MJ has adaptogenic-like activity in rats exposed to UCMS, which may be related to modulation of the purinergic signaling pathway.

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