bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astaxanthin and Olive Oil Pretreatment Improves Recovery of Motor and Cognitive Skills in a Closed Head Injury TBI Model in Male Sabra Mice
Authors: Fleischmann Chen , Shohami Esther , Heled Yuval , Horowitz Michal 
Published: June 2021

Impact related traumatic brain injury (TBI) commonly influences high‐risk populations such as contact sports athletes and combat soldiers. Recovery results in mild to severe loss of motor and cognitive function. Prophylactic protection to enhance resilience and improve the rate and extent of recovery by nutrient supplementation is currently limited. Astaxanthin is a natural xantophyll carotenoid supplement which readily crosses the blood brain barrier (BBB) and was previously shown to improve recovery in a brain ischemia‐reperfusion model when administered post injury.The study objective was to examine the effects of Astaxanthin pre‐supplementation on the motor and cognitive aspects of recovery from a closed head injury (CHI) model in mice.Methodsmale sabra mice were treated with Astaxanthin 100 mg/Kg per day in olive oil by gavage (XO), or olive oil (O) or in pellet form as 1% Astaxanthin in animal food by free eating (X) for 2 weeks, exposed to a CHI model, and followed over a one month recovery period. Motor skills were assessed using the neurological severity score (NSS) at 1, 24, 48, and 72 hours and weekly post injury. Cognitive skills were assessed using the Open filed, and Y‐Maze tests on days 2 and 29 post injury, and the novel object recognition (ORT) test on days 3 and 30 post injury.Ethics: all animal experiments were approved by the Hebrew University authority for biological and biomedical models ethical review board (registration numbers: MD‐13‐13734‐4 & MD‐16‐14842‐4).ResultsNSS scores revealed a significant improvement in motor skills recovery (ΔNSS=1.25±0.16 vs. 0.5±0.27 in XO vs. O, respectively, p=0.001), which began on week 2 and lasted to 4 w. Additional cognitive improvement was demonstrated in the Y‐maze on Day 29: 44.57±3.22% vs. 36.46±1.95% of exploration time spent in the novel arm for XO vs. O, respectively, p=0.03). The results of the open field and ORT tests did not significantly differ between groups.When Astaxanthin supplementation was administered in pellet form (X), a considerably smaller influence was observed in the NSS compared to XO, while cognition (open field, Y‐Maze, ORT) remained unaffected. Post injury X supplementation with or without pre supplementation did not improve results.ConclusionResults suggest an advantage to XO over X and O in motor and cognitive skills recovery. The results of the effect of XO on NSS and on cognitive function, versus the lack of similar motor and cognitive effects with X, suggest a contribution of the combined XO administration to motor and cognitive parameters and warrants further work to elucidate its mechanism as well as the effects of post injury XO supplementation.Support or Funding InformationThis work was funded by the IDF medical corps research authorityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Conditioned Place Preference of Mice Selectively Bred for High Voluntary Wheel Running
Authors: Schmill Margaret P. , Cadney Marcell D. , Hiramatsu Layla , Albuquerque Ralph , Buenaventura Darrius G. , Louis Monica P. , Castro Alberto A. , Thompson Zoe , Kay Jarren C. , Ramirez Jocelyn L. , Garland Theodore 
Published: June 2021

Running acts as a natural reward and shares features with other rewarding behaviors, such as eating or taking drugs of abuse. Exercise is even proposed to have addictive properties, as humans and rodents have shown signs of “withdrawal,” including anxiety and depression, after being denied exercise. Conditioned place preference (CPP) is a neuro‐behavioral test of reward and reinforcement, widely used in studies of addictive processes in rodents. In typical protocols, individuals receive a reward (e.g., cocaine injection) paired with a specific environment (usually a specific floor texture) several times and are then tested for preference of the conditioned environment as compared with a different environment in which they had not received a reward (e.g., saline injection). We studied CPP in a unique exercise model of 4 replicate lines of mice selectively bred for high voluntary wheel running (High Runner or HR lines) and 4 non‐selected control (C) lines. HR mice run ~3‐times as much as C mice on a daily basis, partly because of evolutionary changes in their reward and motivational systems. We hypothesized that HR mice would differ from C in the extent to which they show a CPP following conditioning with rewarding drugs and/or wheel running. In experiment 1, HR and C mice were tested for CPP with cocaine as the reward. Both HR and C mice were significantly conditioned by cocaine, with no statistical difference between groups in the degree of conditioning. In experiment 2, mice were tested for CPP with wheel access as the reward. Specifically, mice were granted or not granted wheel access for 10 days, and each day removed from wheels or standard cages during peak wheel running and placed in CPP chambers for 30 minutes. Preliminary results show no significant conditioning by either HR or C mice. In a recent experiment 3, mice were tested for CPP with Ritalin as the reward, following the same protocol as experiment 1. Functioning as a dopamine transporter blocker, the drug Ritalin has been shown to decrease wheel running of HR mice while increasing running by C mice. Thus, we hypothesize a significant difference in the degree of conditioning between HR and C mice with Ritalin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Spinal Conversion of Testosterone to Estradiol for the Expression of Phrenic Long‐term Facilitation in Adult Male Rats
Authors: Dougherty Brendan J. , Tyurina Elena , McIntosh Danielle 
Published: June 2021

Estrogen modulates the expression of neuroplasticity, including phrenic long‐term facilitation (pLTF), a persistent increase in phrenic nerve activity observed after acute exposure to intermittent hypoxia (AIH; three 5 min episodes of 10.5% O2, delivered at 5‐minute intervals). Though robustly expressed in adult males, adult female rats express pLTF only in the presence of adequate circulating estradiol (E2); removal of the ovaries, the primary source of circulating E2, abolishes pLTF. Acute, spinal application of membrane‐impermeable E2 (E2‐BSA) restores plasticity in ovariectomized female rats through a fast‐acting cellular mechanism involving membrane‐associated estrogen receptors, suggesting spinal E2 signaling may be important for pLTF expression in females. Previous studies indicate that E2 may play an important role in the expression of AIH‐induced pLTF in adult male rats as well. Specifically, gonadectomy blunts pLTF expression by reducing circulating testosterone, and systemic testosterone replacement restores pLTF. However, this testosterone‐induced restoration of pLTF is only effective in the presence of aromatase, an enzyme that converts testosterone to E2. Here we tested the hypothesis that the relevant conversion of testosterone to E2 necessary for expression of pLTF in male rats occurs in the spinal cord near phrenic motor neurons. We recorded phrenic nerve activity and pLTF expression in anesthetized, paralyzed and ventilated male Sprague‐Dawley rats (3–4 mos) in the presence or absence of intrathecally delivered Letrozole, an aromatase inhibitor, over the cervical spinal cord. We combined these data with immunohistochemical characterization of aromatase expression in the ventral cervical spinal cord. Collectively, these data provide important information regarding the necessity for spinal E2 signaling in the expression of AIH‐induced pLTF in male rats, and underscore the utility of this model to dissect the role of E2 signaling in expression of spinal neuroplasticity.Support or Funding InformationFunding: This work was supported by the University of Minnesota Division of Physical Therapy with a generous contribution from the University of Minnesota Department of Rehabilitation Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lack of Uncoupling Protein 3 Protects from High‐Fat Diet‐Induced Insulin Resistance and Glucose Intolerance in Rats
Authors: Lomax Tyler M. , Wiseman Jessica M. , Edwards Kristin S. , Ashraf Sadia , Harmancey Romain 
Published: June 2021

Uncoupling protein 3 (UCP3), a mitochondrial anion carrier regulating fatty acid metabolism, is down‐regulated in type 2 diabetes. Whether UCP3 decrease influences the development of obesity and insulin resistance is currently unclear. We investigated the effect of genetically‐induced partial (UCP3+/−, with a 50% decrease in protein levels) or total (UCP3−/−) deficiency in whole body UCP3 on metabolic fitness in rats. Two lines of UCP3 deficient rats (hereinafter referred to as 1‐bpINS and 22‐bpDEL) were independently generated on a Sprague Dawley background strain using CRISPR‐Cas9 genome editing. Male UCP3 deficient rats and their wild type littermates were maintained on a chow diet or fed a high‐fat diet (HFD) for 14 weeks starting at 8 weeks of age. Metabolic fitness was assessed by analyzing body composition with EchoMRI and by performing insulin and glucose tolerance tests. Although both rat lines had similar lean‐to‐fat ratio and body mass under normal feeding conditions, the 22‐bpDEL line had higher circulating levels of lipids, insulin, and leptin, and was less insulin sensitive and glucose tolerant than the 1‐bpINS line. Partial or total UCP3 deficiency did not cause changes in body weight gain, body composition, or insulin sensitivity when rats were maintained on a chow diet. However, partial and total UCP3 deficiency increased glucose clearance at 15 min following intraperitoneal glucose injection in both rat lines. Compared to chow diet, high‐fat feeding significantly increased weight gain and fat mass while simultaneously impairing insulin sensitivity and glucose tolerance in both rat lines. In the 1‐bpINS line, loss of UCP3 decreased fat mass gain without altering food consumption so that UCP3−/− rats presented higher lean‐to‐fat ratio compared to wild type littermates. Loss of UCP3 improved insulin sensitivity in HFD‐fed 1‐bpINS rats, with a protective effect that was more prominent in UCP3−/− than in the UCP3+/− animals. Likewise, the gradual loss of UCP3 improved glucose tolerance in 1‐bpINS rats and prevented the increase of the glucose area under the curve (AUC) for UCP3−/− rats when compared to chow‐fed values (AUC 20219 vs. 15667 for wild type, P < 0.0001; AUC 18724 vs. 15376 for UCP3+/−, P < 0.01; AUC 17224 vs. 15007 for UCP3−/−, P = 0.4). This improvement of metabolic fitness associated with UCP3 deficiency was absent in rats from the 22‐bpDEL line. In conclusion, loss of UCP3 unexpectedly preserves metabolic fitness in male rats under high‐fat feeding. This protective effect depends on genetic background.Support or Funding InformationSupported by grants R00 HL112952, P01 HL051971, and P20 GM104357 from the National Institutes of HealthThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A pilot study on the effects of hormonal contraceptives on beta‐arrestin1 levels in peripheral blood mononuclear leukocytes
Authors: Smith Keisha , Rana Tanu , Archibong Anthony E. , Nayyar Tultul 
Published: June 2021

OBJECTIVEWomen are twice as likely as likely as men to develop depression during reproductive years. Use of hormonal contraceptives, during reproductive years, may be causal with development of depression in a subgroup of women because observational studies indicate an association between use of progestin (Depo‐Provera) and development of depressive symptoms. Previously we have reported reduced levels of beta arrestin 1(β‐AR‐1) during premenstrual depressive disorder, may be a potential biomarker of depression. In this study we compared the β‐AR‐1 protein levels and the Hamilton Depression Rating Scores (HDRS) as well, in women on non‐hormonal contraceptives (control), combine‐only contraceptives (COC), and progestin‐only contraceptives (POC).METHODSStudy participants (n=29) were non‐pregnant women between 18–42 years of age, not taking any antidepressants/therapy and at the luteal phase of menstruation. The participants were evaluated with Neuropsychiatric Interview (DSMIV‐TR). The severity of depression were determined by the HDRS. The protein levels of beta‐arrestin1 in the in peripheral blood mononuclear leukocytes (PBMC) were determined by ELISA.RESULTSThe magnitude of the different parameters for Axis 1 mental disorders were significantly higher and beta arrestin1 protein levels in PBMC were significantly lower in women currently using progestin‐only contraceptives as compared to the control.CONCLUSIONThese findings indicate the possibility of reduced levels of β‐AR‐1 and associated symptoms of depression in a subgroup of women may results from the use of POC.Support or Funding InformationClinical Research Education and Career Development in Minority R25RR17577 (NCRR/NIMHD) and U54 MD007593 (NIMHD) and U54 RR026140 (NCRR) at NIH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex‐Related Effects of Nesfatin‐1 in the Pituitary
Authors: Schnell Abigayle Lyn , Pate Alicia , Samson Willis K. , Yosten Gina LC. 
Published: June 2021

Neuroendocrine interaction between the hypothalamus, pituitary, and adrenal glands, known as the HPA axis, is responsible for regulation of the adaptive stress response. Nesfatin‐1, a potent anorexigenic peptide expressed in the hypothalamus, has been shown to play a role in the stress response by modulating HPA axis activity in rats. However, elucidation of nesfatin‐1's cognate receptor is necessary to assess the physiological relevance of these findings. Previous data on the nesfatin‐1 signaling pathway indicate involvement of a G‐protein‐coupled receptor. Furthermore, because the stress‐response is known to be sexually dimorphic, we hypothesized that the action and expression of nesfatin‐1 would be influenced by sex hormones. In cultured male rat pituitary cells, treatment with nesfatin‐1 elicits a robust cFos response, but no significant response was observed in female rat pituitary cells. In addition, expression of nesfatin‐1 in the female rat hypothalamus differed across stages of the estrus cycle. To determine the physiological relevance of nesfatin‐1's effects, we also began screening cell lines responsive to nesfatin‐1 for orphan GPCR expression to search for a candidate receptor. These studies suggest that both expression and function of nesfatin‐1 are regulated by sex hormones. Identification of the nesfatin‐1 receptor would potentially yield a novel therapeutic target for stress‐related disorders.Support or Funding InformationNIH HL121456This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
PARTIAL PROGESTERONE DEPRIVATION ALTERS THE TRANSCRIPTION OF ESTROGEN RECEPTORS AND THEIR DOWNSTREAM GENES IN RAT PLACENTAS
Authors: Albader Maie , El‐Farra Aseel , Narayana Kilarkaje 
Published: June 2021

ObjectiveTo investigate the role of progesterone in placental growth and effects on the expression of estrogen receptors‐alpha and ‐beta and their downstream genes.Materials and MethodsPregnant SD rats were segregated into A) control (peanut oil, twice daily injections), B) ovariectomized on 15 day gestation (dg), with progesterone restoration, and C) progesterone reduction groups. To restore estrogen levels, estradiol was administered subcutaneously using mini‐osmotic pump (40 ng/h) and then injected to maintain normal increase in plasma levels of the hormone. In group B, progesterone level was restored by administering the hormone daily and, in group C, progesterone reduction (partial deprivation) to one third of the normally observed level of the hormone on 22 dg was maintained. Placentas were harvested on 19 dg and 21 dg and dissected into basal and labyrinth zones. Gene expression of estrogen receptors‐alpha and ‐beta, p53, Bax and Bcl‐2 was analyzed by real time‐polymerase chain reaction. Data were analyzed by one way ANOVA and Least square difference test with the level of significance set p<0.05.ResultsPartial progesterone deprivation decreased placental and basal zone weights on 19 dg (p<0.05), which was not restored by progesterone restoration to normal levels. Progesterone restoration did not recover decreased fetal body weights in overiectomized rats although placental efficiency was not affected on 21 dg. Partial progesterone deprivation increased the transcription of both estrogen receptors in the basal zone on 19 dg (p<0.05), which recovered to normal levels after progesterone restoration. Similarly, p53, Bax and Bcl‐2 gene expressions were also increased in the basal zones in partial progesterone deprived rats, which were restored to normal levels on 19 dg and 21 dg, after progesterone restoration. A similar pattern was seen in the labyrinth zone on 16 dg and 19 dg.ConclusionPartial progesterone deprivation inhibits placental and fetal growth most probably by enhancing estrogen receptor‐mediated up‐regulation of apoptosis in placentas. Progesterone is essential for normal growth of placentas and fetuses in rats.Support or Funding InformationKuwait University Research Grant # MY02/08This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiovascular Susceptibility in Offspring After Maternal Engineered Nanomaterial Exposure
Authors: Stapleton Phoebe 
Published: June 2021

Cardiovascular disease (CVD) is the leading cause of death worldwide and associated with many genetic and lifestyle risk factors. The maternal health and fetal milieu during gestation has been explored as a contributing factor to progeny health. Engineered nanomaterials (ENM) are manufactured within the nanoscale (<100 nm in one dimension) to take advantage of specific physiochemical properties. Exposure to these materials has become more prolific given their pervasiveness in domestic applications, yet the outcomes during pregnancy and for developing young are currently unknown. Gestational ENM exposure led to impairments in uterine microvascular reactivity in early studies, indicative of the development of a hostile gestational environment. The Barker Hypothesis theorizes that development is such an environment will influence cardiovascular health later in life.Studies were initiated to assess the cardiovascular health during growth from a late‐stage fetus to young adult after maternal ENM inhalation. Pregnant, healthy Sprague‐Dawley rats were exposed to nano‐sized titanium dioxide aerosols (10.4±0.1 mg/m3 for 4h, aerodynamic diameter of 136.5±1.4 nm, calculated daily pulmonary deposition of 39.7±1 μg, initiated on gestational day [GD] 5.78±0.13 for 7.78±0.26 days of the remaining pregnancy). As indices of litter health, the number of fetal pups on GD 20 did not differ between control and exposed (12.2±0.9 vs. 10.8±1.5); however, the size of the placenta (0.76g±0.02 vs. 0.68±0.02) and number of surviving pups (11±0.7 vs. 6±1) were significantly different. As microvascular health can characterize early cardiovascular health, reactivity was assessed via a pressurized isolated microvessel preparation where the arterioles of the tail (fetal [GD 20], neonate [6±0.48d] or heart (weanling [25.7±0.9d], juvenile [7.64±0.4w], adult [10.36±0.34w]) progeny were dissected, excised, and evaluated in response to chemical stimuli to calculate endothelium‐dependent (acetylcholine [10−9–10−4 M]), ‐independent (spermine‐NONOate [10−9–10−4 M]), and vascular smooth muscle (phenylephrine [10−9–10−4 M]) function. Significant temporal impairments in endothelium‐dependent reactivity were identified in exposed fetal (−37.2%±7.3), juvenile (−29.1%±11.3), and adult (−59.3%±17.1 vs. control, respectively) progeny. Further, studies of mitochondrial stress reveal significant reductions in calculated ATP production of isolated cardiomyocytes during development where fetal (23%±3), neonate (83%±3), weanling and juvenile (63%±9), and young adult (75%±2) measurements are below control. Overall, exposure to ENM during gestation may increase CVD susceptibility, thereby compromising health of future generations.Support or Funding InformationNIH‐R00‐ES024783 (PAS); P30‐ES005022This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Early life stress (ELS) protects against LNAME hypertension‐induced renal tubular damage
Authors: Obi Ijeoma , Pollock David , George James , Pollock Jennifer 
Published: June 2021

In humans, early life stress (ELS) is a newly recognized cardiovascular disease risk factor and associated with increases in inflammation and risk of hypertension. Utilizing a rat model of ELS, maternal separation (MatSep), we recently reported that MatSep induced immune activation in the kidney compared to normally‐reared control animals. Chronic nitric oxide synthase blockade with LNAME in the drinking water is a model of hypertension with increased immune cells and inflammation. Therefore, we hypothesized that exposure to MatSep during early life and LNAME during adulthood would induce increased levels of renal injury markers and immune cells when compared to normally‐reared rats with LNAME during adulthood. MatSep involves separating rat pups from the dam for 3hrs/day from postnatal day 2 (PD2) to PD14. Normally‐reared littermate rats were used as controls. Twelve weeks old adult (n=6–8rats/group) control and MatSep rats were given LNAME (100mg/kg/rat) in drinking water for 7 days. LNAME was adjusted daily based on the amount of water intake. We compared urinary renal damage markers and renal immune cell populations in control and MatSep rats after LNAME treatment. On day 7 after LNAME, urine was collected for assessment of glomerular (albumin and nephrin) and tubular (KIM1 and NGAL) injury markers by enzyme‐linked immunosorbent assay (ELISA). Our results showed that urinary KIM1 excretion was significantly lower in MatSep rats compared to control rats (control LNAME vs. MatSep LNAME: 6.78mg/day ± 0.32 vs. 5.53mg/day ± 0.36; p = 0.029). No statistical differences were observed in urinary NGAL, albumin and nephrin excretion. At day 7 after LNAME, blood and kidneys were used for determination of immune cell populations by flow cytometry. The proportion of renal total T cells, T helper cells, macrophages, neutrophils, natural killer, and dendritic cells were similar in control and MatSep rats. However, there was a trend towards an increase in the proportion of cytotoxic T cells in MatSep compared to control animals (%CD45+ cells; control LAME vs. MatSep LNAME: 14.04 ± 0.97 vs. 17.37 ± 1.35; p = 0.087). No differences were observed in the proportion of circulating immune T helper cells, cytotoxic T cells, macrophages, neutrophils, natural killer, and dendritic cells in control and MatSep rats. Our findings suggest that MatSep during early life may protect from tubular injury in response to inhibition of nitric oxide synthase. Future studies are warranted to determine whether the observed renal tubular protection is linked to LNAME induced blood pressure elevation, loss of tubular nitric oxide production, and T cell activation.Support or Funding InformationFunded by Cardiovascular Pathophysiology NIH/NHLBI T32HL007918‐19 to IEO, R01DK059600 to JFG, and P01HL69999 to JSP.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.