The effects of early life stress on context fear generalization in adult rats.

2019 ◽  
Vol 133 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Nathalie D. Elliott ◽  
Rick Richardson
Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Analia S Loria ◽  
Michael W Brands ◽  
David M Pollock ◽  
Jennifer S Pollock

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.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Carmen De Miguel ◽  
Dao H Ho ◽  
Analia S Loria ◽  
Ijeoma Obi ◽  
Jennifer S Pollock

We previously reported that maternal separation (MatSep), an animal model of early life stress, sensitizes rats to pro-hypertensive stimuli in adulthood. We hypothesized that MatSep induces a renal pro-inflammatory immune response. Immune cell populations and expression of cytokines were assessed by magnetic bead isolation, FACS analysis, ELISA and RT-PCR in adult male MatSep and normally-reared littermate control rats. Circulating and renal mononuclear or T cell numbers were similar between control and MatSep rats (n=4-11/group, p>0.05). Both groups presented similar percentages of circulating macrophages and T H , T C , and T reg cells (n=4, p>0.05). However, the percentage of circulating B cells was significantly decreased in MatSep rats (23.7±1.2% vs. 20.1±0.7%; n=4, p<0.05). Pro-inflammatory cytokine IL-1Beta was significantly elevated in kidneys from MatSep rats (4.4±0.5 vs. 7.9±1.0 pg/mg prot; n=7-8/group; p<0.05). However, IFN-gamma, IL-6, and IL-4 were not different between control and MatSep rats. To further assess the immune system in MatSep and control rats, we acutely challenged adult rats with lipopolysaccharide (LPS; 2 mg/kg; i.v., 14 h). LPS significantly elevated renal expression of pro-inflammatory chemokine receptors (CCR3, CCR4, CXCR4), cytokines (IFN-gamma, CCL3, CCL4, IL-16), and activation markers (CD40, CD40lg) in MatSep rats (4 to 6 fold increase; n=5/group, p<0.05), suggesting that MatSep induces an exaggerated pro-inflammatory renal immune response to LPS. In conclusion, early life stress induces a renal pro-inflammatory status in adulthood that leads to sensitization to further immune challenges. Funded by P01 HL 69999 to JSP, NIH T32 DK007545 to CDM, F32 HL 116145 to DHH and K99/R00 HL 111354 to ASL.


2019 ◽  
Vol 29 ◽  
pp. S405
Author(s):  
N. Broshevitskaya ◽  
I. Pavlova ◽  
M. Zaichenko ◽  
V. Gruzdeva ◽  
G. Grigoryan

2019 ◽  
Vol 372 ◽  
pp. 112025 ◽  
Author(s):  
Dmitry Frank ◽  
Alexander Zlotnik ◽  
Ora Kofman ◽  
Julia Grinshpun ◽  
Olena Severynovska ◽  
...  

2021 ◽  
Vol 17 ◽  
pp. 174480692110229
Author(s):  
Paul G Green ◽  
Pedro Alvarez ◽  
Jon D Levine

Adult rats that experienced neonatal limited bedding (NLB), a form of early-life stress, experience persistent muscle mechanical hyperalgesia. Since there is a growing recognition that the gut microbiome regulates pain and nociception, and that early-life stress produces a long-lasting impact on the gut microbiome, we tested the hypothesis that persistent muscle hyperalgesia seen in adult NLB rats could be ameliorated by interventions that modify the gut microbiome. Adult NLB rats received probiotics, either Lactobacillus rhamnosus GG (10 billion CFU/150 ml) or De Simone Formulation (DSF) (112.5 billion CFU/150 ml mixture of 8 bacterial species), in their drinking water, or non-absorbable antibiotics, rifaximin or neomycin, admixed with cookie dough, to provide 50 mg/kg. Mechanical nociceptive threshold in the gastrocnemius muscle was evaluated before and at several time points after administration of probiotics or antibiotics. Adult NLB rats fed probiotics L. Rhamnosus or DSF, antibiotics, as well as rats fed non-absorbable antibiotics rifaximin or neomycin, had markedly attenuated muscle mechanical hyperalgesia. We hypothesize that persistent skeletal muscle hyperalgesia produced by NLB stress may be, at least in part, due to a contribution of the gut microbiome, and that modulation of gut microbiome using probiotics or non-absorbable antibiotics, may be novel therapeutic approaches for the treatment of chronic musculoskeletal pain.


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