scholarly journals Assessment of the Central Effects of Natural UraniumviaBehavioural Performances and the Cerebrospinal Fluid Metabolome

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
P. Lestaevel ◽  
S. Grison ◽  
G. Favé ◽  
C. Elie ◽  
B. Dhieux ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Drinking Water ◽  
Locomotor Activity ◽  
Brain Function ◽  
Spatial Working Memory ◽  
Natural Uranium ◽  
Female Rats ◽  
Male Rats ◽  
The Central Nervous System ◽  
And Control

Natural uranium (NU), a component of the earth’s crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NUvialactation and drinking water (1.5, 10, or 40 mg·L−1for male rats and 40 mg·L−1for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg·L−1NU. In male rats, spatial working memory and anxiety- and depressive-like behaviour were only altered by exposure to 40 mg·L−1NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function.

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. II. Behavioral and Neurodevelopment Effects

2005 ◽  
Vol 24 (6) ◽  
pp. 451-467 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
Michael F. Girard ◽  
David R. Mattie ◽  
Marni V. K. Bekkedal ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Brain Regions ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Continuous Access ◽  
Brain Morphometry ◽  
The Central Nervous System ◽  
The Right

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

scholarly journals Developing the Concepts of Homeostasis, Homeorhesis, Allostasis, Elasticity, Flexibility and Plasticity of Brain Function

NeuroSci ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 372-382
Author(s):  
Alfredo Pereira
Keyword(s):  
Brain Function ◽  
Complex Dynamics ◽  
Stable States ◽  
Set Point ◽  
Brain Functions ◽  
Temporal Phase ◽  
The Central Nervous System ◽  
Elastic Processes ◽  
And Control ◽  
Flexible Processes

I discuss some concepts advanced for the understanding of the complex dynamics of brain functions, and relate them to approaches in affective, cognitive and action neurosciences. These functions involve neuro-glial interactions in a dynamic system that receives sensory signals from the outside of the central nervous system, processes information in frequency, amplitude and phase-modulated electrochemical waves, and control muscles and glands to generate behavioral patterns. The astrocyte network is in charge of controlling global electrochemical homeostasis, and Hodgkin–Huxley dynamics drive the bioelectric homeostasis of single neurons. In elastic processes, perturbations cause instability, but the system returns to the basal equilibrium. In allostatic processes, perturbations elicit a response from the system, reacting to the deviation and driving the system to stable states far from the homeostatic equilibrium. When the system does not return to a fixed point or region of the state space, the process is called homeorhetic, and may present two types of evolution: (a) In flexible processes, there are previously existing “attractor” stable states that may be achieved after the perturbation, depending on context; (b) In plastic processes, the homeostatic set point(s) is(are) changed; the system is in a process of adaptation, in which the allostatic forces do not drive it back to the previous set point, but project to the new one. In the temporal phase from the deviant state to the recovery of stability, the system generates sensations that indicate if the recovery is successful (pleasure-like sensations) or if there is a failure (pain-like sensations).

scholarly journals Reversal of Diet-Induced Obesity Increases Insulin Transport into Cerebrospinal Fluid and Restores Sensitivity to the Anorexic Action of Central Insulin in Male Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1047-1054 ◽  
Author(s):  
Denovan P. Begg ◽  
Joram D. Mul ◽  
Min Liu ◽  
Brianne M. Reedy ◽  
David A. D'Alessio ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Food Intake ◽  
High Fat Diet ◽  
Male Rats ◽  
Control Group ◽  
Chow Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Insulin Transport ◽  
The Central Nervous System

Abstract Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport. Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD). After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18). The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group. Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats. Fasting cerebrospinal fluid insulin was higher in DIO than Con animals. However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group. These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin's transport to the CNS. Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.

scholarly journals Oestrogenic effects of neonatal administration of raloxifene on hypothalamic-pituitary-gonadal axis in male and female rats

Reproduction ◽  
2001 ◽  
pp. 915-924 ◽  
Author(s):  
L Pinilla ◽  
LC Gonzalez ◽  
F Gaytan ◽  
M Tena-Sempere ◽  
E Aguilar
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Oestrogen Receptor ◽  
Female Rats ◽  
Male Rats ◽  
Selective Oestrogen Receptor Modulators ◽  
Male And Female Rats ◽  
The Central Nervous System ◽  
Neonatal Administration

Selective oestrogen receptor modulators constitute a family of drugs that are used increasingly in the management of oestrogen-associated pathology. Raloxifene is a selective oestrogen receptor modulator that is used to treat and prevent osteoporosis in post-menopausal women. The actions of raloxifene on bone, breast, uterus and serum cholesterol concentrations have been widely analysed, but very few studies have investigated the possible actions of this drug on the central nervous system. The central nervous system of the newborn rat is very sensitive to oestrogen action. In this study a series of experiments was conducted to analyse the effects of different doses of raloxifene (50, 100, 250 or 500 microg per rat per day) administered to neonatal rats on days 1-5 of age. Female rats treated with raloxifene showed decreased gonadotrophin secretion, hyperprolactinaemia, advanced vaginal opening, decreased body weight, persistent presence of cornified epithelial cells in vaginal smears, anovulation, inhibition of positive feedback between oestradiol and LH, and infertility. Male rats showed delayed balanopreputial separation, reduced body weight and hyperprolactinaemia. All these changes resemble those obtained after neonatal administration of oestradiol benzoate, thus indicating, for the first time, that raloxifene exerts an oestrogenic action on the hypothalamic-pituitary structures controlling reproductive function in rats.

N-(3,5-dinitrophenyl)-5-methoxytryptamine, a novel melatonin antagonist: effects on sexual maturation of the male and female rat and on oestrous cycles of the female rat

1988 ◽  
Vol 116 (1) ◽  
pp. 43-53 ◽  
Author(s):  
M. Laudon ◽  
Z. Yaron ◽  
N. Zisapel
Keyword(s):  
Drinking Water ◽  
Adult Female ◽  
Sexual Maturation ◽  
Young Male ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Simultaneous Administration ◽  
Serum Concentrations ◽  
The Brain

ABSTRACT N-(3,5-dinitrophenyl)-5-methoxytryptamine (ML-23) has recently been synthesized and shown to antagonize the inhibitory effect of melatonin on the release of dopamine in vitro from the hypothalamus of female rats. In the present study the ability of ML-23 to inhibit in vivo the following melatonin-mediated effects was investigated: (1) delayed sexual maturation of young male rats, (2) delayed sexual maturation of young female rats, (3) inhibition of ovulation in mature female rats and (4) re-establishment of oestrous cycles in adult female rats maintained in continuous light. The inhibitory effect of daily melatonin injections, given in the afternoon, on the growth of the prostate gland and seminal vesicles and on serum testosterone concentrations in young male rats was prevented by daily injections of ML-23. Daily injections of ML-23 alone did not affect sexual maturation of young rats. In young male rats treated through the drinking water with melatonin, the growth of the accessory sex organs, but not that of the testes, was delayed and serum concentrations of testosterone were lower than in untreated rats. Administration of ML-23 through the drinking water increased serum concentrations of testosterone but did not significantly affect the weights of the accessory sex organs. Simultaneous administration of ML-23 and melatonin through the drinking water prevented completely, in a dose-dependent manner, the melatonin-mediated decrease in epididymal weights and in serum concentrations of testosterone and partially inhibited the delayed growth of the prostate glands and seminal vesicles. In young female rats treated with melatonin through the drinking water for 30 days, the growth of the ovaries was inhibited and serum concentrations of oestradiol were lower than in untreated rats. The growth of the uterus was not significantly affected. Administration of ML-23 through the drinking water did not significantly affect uterine and ovarian weights or oestradiol concentrations. Simultaneous administration of melatonin and ML-23 through the drinking water prevented completely the melatonin-mediated decrease in ovarian weights and in serum oestradiol concentrations. Ovulation during presumptive oestrus was prevented in adult female rats treated through the drinking water for 7 days with melatonin. Administration of ML-23 alone did not significantly affect the average numbers of ova shed and corpora lutea present. Simultaneous administration of ML-23 and melatonin prevented completely the melatonin-mediated inhibition of ovulation; the average number of ova shed was the same as in controls. Suppression of reproductive cycles occurred in adult female rats after long-term exposure to continuous light. This suppression was prevented by daily injections of melatonin in the afternoon; the incidence of constant oestrus decreased by 80%. Simultaneous injection of ML-23 and melatonin into rats maintained under continuous illumination prevented the effect of melatonin, and all the animals remained in constant oestrus. Administration of ML-23 alone did not alter the incidence of constant oestrus. A tritium-labelled derivative of ML-23 was prepared and administered orally to male rats. Peak concentrations of ML-23 occurred in the blood within 30 min after feeding and disappeared subsequently with a half-life of about 42 min. Intraperitoneal injection of [3H]ML-23 resulted in the appearance of peak concentrations of the drug in the brain within 20 min. The effects of ML-23 on serotonin S1 and S2 receptors, dopamine D2 receptors and melatonin receptors in the brain of the male rat were investigated using [3H]serotonin, [3H]spiperone and 2-[125I]iodomelatonin respectively. The binding of [3H]serotonin to brain synaptosomes and of [3H]spiperone to synaptosomes prepared from the cortical and caudate regions of the cerebrum was unaffected by ML-23 (10 μmol/l), whereas the binding of 2-[125I]iodomelatonin to brain synaptosomes was entirely inhibited. The results demonstrate the potency of ML-23 in antagonizing melatonin-mediated effects in the male and female rat in vivo. The drug may be administered to the animals simply through the drinking water, for relatively long periods without apparent deleterious effects on survival and welfare. ML-23 is accessible to both central and peripheral sites and acts specifically on melatonin but not on serotonin or dopamine receptors in the brain. The availability of a melatonin antagonist offers new opportunities for exploring the physiological role of melatonin in the neuroendocrine system. J. Endocr. (1988) 116, 43–53

Sex as a determining factor in the effect of exercise on in vivo autoimmune response adjuvant arthritis

1994 ◽  
Vol 76 (3) ◽  
pp. 1172-1175 ◽  
Author(s):  
A. Ferry ◽  
C. Le Page ◽  
M. Rieu
Keyword(s):  
Adjuvant Arthritis ◽  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
Autoimmune Response ◽  
Human Rheumatoid Arthritis ◽  
Control Female ◽  
And Control ◽  
Arthritic Joints

The present study was conducted to examine the effect of physical exercise on the development of adjuvant arthritis (AA), an animal model of the human rheumatoid arthritis, which is a T-cell-dependent autoimmune response. AA was inducted on day 0 in 8-wk-old Lewis rats of both sexes. Between postinjection days 1 and 12, two groups of rats (male and female) were trained on a treadmill every day (45–120 min/day and 15–30 m/min) before the onset of arthritic disease. Trained female (n = 27) and male (n = 22) rats and control female (n = 29) and male (n = 17) rats were observed every 2 days for the following clinical signs of AA: number of arthritic joints (swelling and redness), paw thickness, and weight gain during the disease. The results show that the incidence of arthritis (% of arthritic rats) was significantly higher in trained female rats (74%; P < 0.03) and significantly lower in trained male rats (27%; P < 0.05) compared with control rats of both sexes (female, 45%; male, 59%). There was no difference in the severity and development of the disease between trained rats and control rats of both sexes (P > 0.05). The present study indicates that the effect of exercise on the incidence of AA, an in vivo autoimmune response, depends on the sex of the animal.

Oral (Drinking Water) Two-Generation Reproductive Toxicity Study of Dibromoacetic Acid (DBA) in Rats

2002 ◽  
Vol 21 (4) ◽  
pp. 237-276 ◽  
Author(s):  
M. S. Christian ◽  
R. G. York ◽  
A. M. Hoberman ◽  
J. Frazee ◽  
L. C. Fisher ◽  
...  
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Female Rats ◽  
Male Rats ◽  
Feed Consumption ◽  
Organ Weights ◽  
Body Weights ◽  
Group Generation ◽  
Generation Male ◽  
F1 Generation

In a two-generation study of dibromoacetic acid (DBA), Crl SD rats (30 rats/sex/group/generation) were provided DBA in drinking water at 0 (reverse osmosis-deionized water), 50,250, and 650 ppm (0,4.4 to 11.6,22.4 to 55.6, and 52.4 to 132.0 mg/kg/day, respectively; human intake approximates 0.1 μg/kg/day [0.0001 mg/kg/day]). Observations included viability, clinical signs, water and feed consumption, body and organ weights, histopathology, and reproductive parameters (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios and viabilities, maternal behaviors, reproductive organ weights, sperm parameters and implantation sites, sexual maturation). Histopathological evaluations were performed on at least 10 P and F1 rats/sex at 0 and 650 ppm (gross lesions, testes, intact epididymis; 10 F1 dams at 0, 250, and 650 ppm for primordial follicles). Developmental observations included implantations, pup numbers, sexes, viabilities, body weights, morphology, and reproductive performance. At 50 ppm and higher, both sexes and generations had increased absolute and relative liver and kidneys weights, and female rats in both generations had reduced absolute and relative adrenal weights; adrenal changes were probably associated with physiological changes in water balance. The livers and kidneys (10/sex/group/generation) had no histopathological changes. Other minimal effects at 50 ppm were reduced water consumption and a transient reduction in body weight. At 250 and 650 ppm, DBA reduced parental water consumption, body weight gains, body weights, feed consumption, and pup body weights. P and F1 generation male rats at 250 and 650 ppm had altered sperm production (retained step 19 spermatids in stages IX and X tubules sometimes associated with residual bodies) and some epididymal tubule changes (increased amounts of exfoliated spermatogenic cells/residual bodies in epididymal tubules, atrophy, and hypospermia), although inconsistently and at much lower incidences. Unilateral abnormalities of the epididymis (small or absent epididymis) at 650 ppm in four F1 generation male rats were considered reproductive tract malformations. The no-observable-adverse-effect level (NOAEL) and reproductive and developmental NOAELs for DBA were at least 50 ppm (4.5 to 11.6 mg/kg/day), 45,000 to 116,000 times the human adult exposure level. Reproductive and developmental effects did not occur in female rats exposed to DBA concentrations as high as 650 ppm. Based on the high multiples of human exposure required to produce effects in male rats, DBA should not be identified as a human reproductive or developmental risk.

THYROTROPHIN RELEASING FACTOR (TRF) IN CEREBROSPINAL FLUID OF THE 3RD VENTRICLE OF RAT

1974 ◽  
Vol 76 (2) ◽  
pp. 209-213 ◽  
Author(s):  
K. M. Knigge ◽  
S. A. Joseph
Keyword(s):  
Cerebrospinal Fluid ◽  
Drinking Water ◽  
Median Eminence ◽  
Cold Exposure ◽  
Male Rats ◽  
Assay Method ◽  
Normal Male ◽  
3Rd Ventricle ◽  
Pooled Samples

ABSTRACT The concentration of TRF in cerebrospinal fluid (CSF) of the 3rd ventricle and content of TRF in median eminence of the rat was examined. CSF (0.3–0.5 μl per animal) was collected from the 3rd ventricle by a microcannula technique and pooled samples from 10–15 animals were examined for TRF using an in vitro pituitary assay method. TRF concentration in 3rd ventricle CSF of normal male rats was 18.5 ± 4.2 pg/μl; median eminence contained 115 ± 12 pg. Cold exposure (4°C) for 16–18 h and thyroxine treatment (2.5 μg/day) for 5 days markedly reduced TRF concentration in CSF and content in the median eminence. Treatment with the anti-thyroid drug methimazole (0.01 % in the drinking water) for 5 days did not notably affect TRF in CSF or median eminence.

scholarly journals Early life stress induces renal dysfunction in adult male rats but not female rats

2013 ◽  
Vol 304 (2) ◽  
pp. R121-R129 ◽  
Author(s):  
Analia S. Loria ◽  
Tatsuo Yamamoto ◽  
David M. Pollock ◽  
Jennifer S. Pollock
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Early Life ◽  
Female Rats ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Ang Ii ◽  
Control Female ◽  
Induced Hypertension ◽  
And Control

Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats.

DEVELOPMENT OF THE MECHANISMS INVOLVED IN THE FACILITATORY AND INHIBITORY EFFECTS OF OVARIAN STEROIDS ON THE RELEASE OF FOLLICLE-STIMULATING HORMONE IN THE IMMATURE RAT

1973 ◽  
Vol 58 (3) ◽  
pp. 547-554 ◽  
Author(s):  
L. CALIGARIS ◽  
J. J. ASTRADA ◽  
S. TALEISNIK
Keyword(s):  
Follicle Stimulating Hormone ◽  
Significant Rise ◽  
Feedback Effect ◽  
Female Rats ◽  
Male Rats ◽  
Facilitatory Effect ◽  
Inhibitory Effects ◽  
Immature Rat ◽  
The Central Nervous System ◽  
Stimulating Hormone

SUMMARY Serum follicle-stimulating hormone (FSH) concentration was found to be higher in neonatal female rats than in adults. The values increased to a maximum on day 15 and decreased thereafter. Ovariectomy soon after birth or at 5 days of age induced a significant rise in serum FSH concentration 9 days later. Administration of 10 μg oestradiol benzoate (OB) lowered FSH concentration in both intact and spayed animals. Progesterone (1 mg) injected 3 days after priming female rats with a single dose of 10 μg OB induced, on the same day, a significant rise in serum FSH concentration in animals older than 22 days of age. In younger animals progesterone reversed the effect of OB. The facilitatory effect of progesterone occurred when the hormone was given in the afternoon but not when it was given in the morning. Male rats, although showing the negative feedback effect of OB injection, failed to show the positive feedback effect of progesterone. It is concluded that the central nervous system—hypophysial mechanism responsible for FSH secretion is ready to function before puberty. In female rats initiation of puberty probably depends on the activation of that mechanism by appropriate facilitatory ovarian steroid signals.

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