scholarly journals Creatine Supplementation Upregulates mTORC1 Signaling and Markers of Synaptic Plasticity in the Dentate Gyrus While Ameliorating LPS-Induced Cognitive Impairment in Female Rats

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2758
Author(s):  
Xuansong Mao ◽  
Taylor J. Kelty ◽  
Nathan R. Kerr ◽  
Thomas E. Childs ◽  
Michael D. Roberts ◽  
...  

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p < 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.

Author(s):  
Taylor J. Kelty ◽  
Xuansong Mao ◽  
Nathan R. Kerr ◽  
Thomas E. Childs ◽  
Gregory N. Ruegsegger ◽  
...  

Neuroinflammation is an early detectable marker of mild cognitive impairment, the transition state between normal cognition and dementia. Resistance-exercise training can attenuate the cognitive decline observed in patients with mild cognitive impairment. However, the underlying mechanisms of resistance training effects are largely unknown. To further elucidate mechanisms of the known cognitive health benefits from resistance-exercise training, we tested if three weeks of resistance-exercise training could ameliorate lipopolysaccharide-induced neuroinflammation. Five-week-old female Wistar rats received intracerebroventricular injections of lipopolysaccharides to induce neuroinflammation and cognitive impairment. Rats then underwent three weeks of progressive ladder climbing to recapitulate resistance-exercise training in humans. Cognition was assessed towards the end of the training period by novelty object recognition testing. Neuroinflammation was measured one and 24-hours after the last resistance-exercise training workout. Resistance-exercise training ameliorated cognitive impairment, diminished lipopolysaccharide-induced neuroinflammatory cytokine expression, and attenuated astrocyte remodeling in the dentate gyrus 24-hours post exercise. Here, we provide evidence that the ladder-climbing model of resistance-exercise training in rats can improve cognition as early as three weeks. Additionally, these data support the hypothesis that resistance exercise can reduce lipopolysaccharide-induced neuroinflammation in the dentate gyrus.


2021 ◽  
Author(s):  
◽  
Taylor Jacob Kelty

Mild cognitive impairment increases risk for dementia. One therapeutic intervention that is reported to ameliorate cognition in patients with mild cognitive impairment is resistance exercise. However, the underlying neuro-molecular mechanisms behind resistance exercise are largely unknown. To better understand the underlying neuro-molecular mechanisms, I established a preclinical model of resistance-exercise training and mild cognitive impairment based off the literature. Ladder climbing in female Wistar rats let to similar increases in muscle mass and strength as those observed in humans, while intracerebroventricular injections of lipopolysaccharides (LPS) induced neuroinflammation and cognitive deficits, which resembled clinical mild cognitive impairment. Resistance-exercise training restored cognitive function, increased IGF-1R phosphorylation and subsequent downstream signaling, and ameliorated neuroinflammation. Selective IGF-1R inhibition in the dentate gyrus, with picropodophyllin, had differential effects on cognition dependent on training status and type of cognition measured. Collectively, these studies indicate that although resistance training and IGF-1 signaling both ameliorate LPS-induced neuroinflammation, IGF-1 signaling during resistance-exercise training, but is only necessary for its ability to ameliorate mild cognitive impairment after a single workout. Furthermore, we made a novel discovery where dentate gyrus IGF-1R inhibition can improve specific forms of cognition. These findings reveal the complexity of IGF-1 signaling and open new areas of study that could offer insights for the treatment of mild cognitive impairment.


1974 ◽  
Vol 75 (3) ◽  
pp. 569-578 ◽  
Author(s):  
G. Buffler ◽  
S. Roser

ABSTRACT The mechanisms involved in the prolongation of the oestrous cycle following LH administration were studied in 4-day cyclic female Wistar rats. In females injected with LH on the morning of dioestrus I there was an increase in ovarian venous blood progesterone as compared with non-injected animals. In both LH-treated females, and those injected with progesterone on the morning of dioestrus I, a slowing up in follicular growth was observed from the afternoon of dioestrus I. The size of follicles greater than 400 urn present in LH or progesterone injected animals on the third day of cycle was similar to the size reached by the same range of follicles in non-injected animals on the second day of the cycle. Hence, the increase in endogenous ovarian progesterone elicited by LH was considered as the cause of the slowing up of follicular growth and therefore of the lengthening of the oestrous cycle duration in female rats injected with LH at the beginning of 4-day cycle.


1990 ◽  
Vol 68 (10) ◽  
pp. 1385-1387 ◽  
Author(s):  
Viviana A. Catania ◽  
Marcelo G. Luquita ◽  
María C. Carrillo ◽  
Aldo D. Mottino

In the present study we analyzed the effect of spironolactone administration on hepatic and intestinal p-nitrophenol-UDP-glucuronyltransferase activity. We used microsomal preparations from male and female Wistar rats to establish whether or not this effect was sex dependent. Enzyme activity was measured in the presence of UDP-N-acetylglucosamine, a presumed physiological activator of the enzyme. Female but not male microsomes showed an increase in enzyme activity of both hepatic and intestinal tissue preparations in response to the inducer pretreatment. In addition, the inducer effect observed in female rats showed a tissue-related difference, since percent increase in the intestinal enzyme activity was greater than that in the liver (127 and 52%, respectively). These results suggest that factors regulating enzyme activity or mechanisms involved in the inducer effect of spironolactone could be different in the intestinal mucosa in comparison to the liver. A possible explanation of sex-related response to spironolactone administration was discussed.Key words: p-nitrophenol, UDP-glucuronyltransferase, spironolactone induction, sex differences.


Parasitology ◽  
1972 ◽  
Vol 64 (3) ◽  
pp. 517-523 ◽  
Author(s):  
D. W. T. Crompton ◽  
D. E. Walters

An analysis of the course of infection of mixed oral infections of 12 cystacanths of Moniliformis dubius in 174 male and 179 female Wistar rats has been undertaken.There was a marked decline in the average recovery rate of worms of both sexes from hosts of both sexes during the course of the infection.Female worms from both male and female rats showed, on average, a greater power of survival than male worms from the third period (10–13 weeks) onwards.Male rats were found to retain, on average, a greater number of worms of both sexes than female rats.We wish to thank Miss Susan Arnold and Mr David Barnard for excellent technical help.


2017 ◽  
Author(s):  
Jacques D. Nguyen ◽  
Yanabel Grant ◽  
Tony M. Kerr ◽  
Arnold Gutierrez ◽  
Maury Cole ◽  
...  

AbstractRationaleA reduced effect of a given dose of Δ9-tetrahydrocannabinol (THC) emerges with repeated exposure to the drug. This tolerance can vary depending on THC dose, exposure chronicity and the behavioral or physiological measure of interest. A novel THC inhalation system based on e-cigarette technology has been recently shown to produce the hypothermic and antinociceptive effects of THC in rats.ObjectiveTo determine if tolerance to these effects can be produced with repeated vapor inhalation.MethodsGroups of male and female Wistar rats were exposed to 30 minutes of inhalation of the propylene glycol (PG) vehicle or THC (200 mg/mL in PG) two or three times per day for four days. Rectal temperature changes and nociception were assessed after the first exposure on the first and fourth days of repeated inhalation.ResultsFemale, but not male, rats developed tolerance to the hypothermic and antinociceptive effects of THC after four days of twice-daily THC vapor inhalation. Thrice daily inhalation for four days resulted in tolerance in both male and female rats. The plasma THC levels reached after a 30 minute inhalation session did not differ between the male and female rats.ConclusionsRepeated daily THC inhalation induces tolerance in female and male rats, providing further validation of the vapor inhalation method for preclinical studies.AbbreviationsPG, propylene glycol; THC; Δ9tetrahydrocannabinol;


2021 ◽  
Vol 4 (4) ◽  
Author(s):  
Sabatina Windyaningrum ◽  
◽  
Tri Yudani Mardining Raras ◽  
Bambang Rahardjo ◽  
Rose Khasana Dewi

Background: kefir is a fermented milk product that demonstrates numerous health benefits including antioxidant and immunomodulatory. Aim: to study the protective effect kefir on the expression of estrogen receptor alpha (ERα) in endometrial stromal cells and endometrial thickness on female rats that were exposed to arsenic. Methods: twenty-five female Wistar rats (Rattus norvegicus) were divided into five groups (CRL, As, T1, T2, T3). Control group (given a normal diet), As group (given the normal diet and exposed to arsenic trioxide 2 mg/kgBW/day). The T1; T2; T3 were exposed to arsenic trioxide 2 mg/kgBW/day and treated with different doses of kefir (1.25; 2.5; and 5 mL/kgBW/day, respectively) for 35 days. The rats of group As treated with arsenic trioxide only and group CRL served as control with normal feed in water. Cytological samples were taken after 35 days of treatment and examined every day to see the rat oestrus phase, and the proestrus phase of the oestrous cycle was chosen for termination. Uterine tissue fixed in 10% neutral buffered formalin for tissue preparation. ERα expression in endometrial stromal cells was analized using immunohistochemistry method, endometrial thickness was observed using histopathological methods. Results: significant reduction of ERα expression in endometrial stromal cells and endometrial thickness in female rats exposed to arsenic were observed in groups on treated rats (p ≤ 0.000; 0.009, respectively). Conclusion: the administration of kefir in female Wistar rats exposed to arsenic had shown significantly differences on ERα expressions and endometrial thickness. The smallest dose of kefir (1.25 mL/kgBW/day) could increase ERα expression and endometrial thickness in female Wistar rats with arsenic exposure. Therefore kefir has protective effect related to female reproductive system.


Author(s):  
Akanksha Awasthi ◽  
Mamta F. Singh ◽  
Saurabh Sharma

Background: Phytoestrogens have recently become a hot topic among scientists. Phytoestrogens’ estrogen-like properties have led to their widespread use in the reproductive system. The aim of this research was to see whether the ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum had any estrogenic activity in female wistar rats. Methods: In female wistar rats, the estrogenic effect was studied using a uterotropic assay, vaginal cytology and vaginal opening. In ovariectomized immature and mature female wistar rats, a 400 mg/kg body weight (b.w.) dose of ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum was given. Result: When compared to ovariectomized control rats, the uterine wet weight increased significantly. The estrogen-treated rats had only cornified epithelial cells, indicating the existence of oestrogen, as well as 100% vaginal opening. At 400 mg/kg b.w., the ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum demonstrated promising estrogenic activity, as evidenced by uterotropic assays, vaginal opening measurements and histopathological changes. As a result of this research, it’s possible to infer that the ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum play an important role in estrogenic activity in female rats.


2015 ◽  
Vol 116 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Markéta Fialová ◽  
Jana Šírová ◽  
Věra Bubeníková-Valešová ◽  
Romana Šlamberová

The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.


2015 ◽  
Vol 6 (2) ◽  
pp. 67-72
Author(s):  
Manizheh Karami ◽  
Fatemeh Lakzaei ◽  
MohammadReza Jalali Nadoushan

ABSTRACT Background and objective Polycystic ovary syndrome (PCOS) can be induced in Wistar rats by over production of nitric oxide (NO). This study evaluated the efficacy of naloxone on the breeding characteristics of rats suffering from nitric oxide induced PCOS. Materials and methods Twenty-four female Wistar rats(200–250 gm) were kept as virgin under standard conditions. They were divided into four groups (n = 6). One group of the animals received L-arginine (50 mg/kg) intraperitoneally (i.p.) for 9 days/once a day. Another group was administered naloxone hydrochloride (0.4 mg/kg, i.p.) prior to injection of L-arginine. The third group was injected solely naloxone. Control group received saline solution (1 ml/kg, i.p.). After the treatments, all female rats were coupled with the intact males. They were then separated by observation of vaginal plaques; it was considered as day 0 of pregnancy. Eventually, they were operated on days 18 to 19 of the gestation to collect the animals’ ovaries. The samples were studied for pathological evidence. The fetal number and weight along with the fetal crown-rump length (CRL) were measured. Results The ovaries obtained from the L-arginine treated group had large cysts with thickened granulosa cell layer in contrast to those of the control or naloxone treated rats (p < 0.0001). The number of fetus though showed a decrease in the L-arginine treated rats (3 ± 1), but the fetal weight or fetal CRL did not change (p > 0.05). Conclusion This study may clearly illustrate the polycystic characteristics in the L-arginine treated group. It may particularly display the breeding efficacy of naloxone in rats with PCOS. How to cite this article Karami M, Lakzaei F, Nadoushan MRJ. Naloxone Breeding Effectiveness in Rat Suffering from Nitric Oxide-induced Polycystic Ovary Syndrome. Int J Infertil Fetal Med 2015;6(2):67-72.


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