Early Neurodevelopmental Anomalies in Young Rats from Adult female Treated with Valproic Acid

Background: the influence of VPA on murine fertility, and on offspring is well documented: VPA decreases the fertility rate (by 25%) and the number of fœtus. Furthermore, VPA causes behavioral alterations in rodents similar to the symptoms observed in autism.Objective: in this study we investigated the effects of exposure of non-pregnant adult rats to VPA in the offspring of these animals.Material and methods: non-pregnant adult rats were divided into 3 groups; (1) distilled water group, (2) VPA 200 mg / kg group and (3) VPA 400 mg/kg group. The products were administered orally daily for 30 days. At the end of treatments, all rats were put into monogamous mating with breeding males. The zootechnical characteristics (gestation period, litter size, mortality rate) were then noted. The young rats were then subjected to a battery of behavioral tests (reversal and anti-gravity reflexes, cliff avoidance, suspension, motor coordination and eye opening), carried out at different stages of life to assess sensorimotor development. Morphological abnormalities were also sought, as well as the mortality rate on the 28th day of life.Results: An increase in the mortality rate and a decrease in the mean lifespan were found in female rats exposed to VPA. Young rats from female rats exposed to VPA showed decreased success rates and performance in behavioral testing. Morphodevelopmental abnormalities such as adictalia or stump necrosis were found in the VPA groups. The offspring mortality rate of female rats exposed to VPA 200 mg/kg was 100%.Conclusion: VPA administered to non-pregnant adult rats causes developmental abnormalities, decreased success rates for performance testing, deformities and increased mortality in young rats from the treated rats by VPA.

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HORMONAL ACTION ON MONOAMINE OXIDASE ACTIVITY IN RATS

Canadian Journal of Biochemistry ◽

10.1139/o67-042 ◽

1967 ◽

Vol 45 (3) ◽

pp. 355-362 ◽

Cited By ~ 30

Author(s):

A. Ho-Van-Hap ◽

L. M. Babineau ◽

L. Berlinguet

Keyword(s):

Monoamine Oxidase ◽

Adult Female ◽

Oxidase Activity ◽

Female Rats ◽

Monoamine Oxidase Activity ◽

Adult Rats ◽

Young Rats ◽

Mao Activity ◽

Hormonal Action

Male young and adult rats were injected with thyroxin, hydrocortisone and puromycin. Monoamine oxidase (MAO) activity was studied in liver, brain, kidney, and heart with L-tryptamine-2-14C as substrate. After thyroxin treatment, heart MAO increased in young animals but decreased in adult animals. Thyroxin decreased liver MAO in adult animals. Brain MAO remained constant in all experiments, whereas kidney MAO showed a slight decrease after thyroxin injection. In young rats, puromycin did not prevent the increase in heart MAO caused by thyroxin injection. Hydrocortisone did not enhance MAO activity in liver, brain and heart. Of all organs studied, only the heart showed a marked increase of MAO with age. In female rats, thyroxin has little effect on brain and liver MAO, whereas it increases MAO activity in the heart of young and adult animals by 67% and 32% respectively. Adult female rats have twice as much heart MAO as males.

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Gender and gonadal influences on ghrelin mRNA levels in rat stomach

Acta Endocrinologica ◽

10.1530/eje.0.1440687 ◽

2001 ◽

pp. 687-690 ◽

Cited By ~ 50

Author(s):

O Gualillo ◽

JE Caminos ◽

M Kojima ◽

K Kangawa ◽

E Arvat ◽

...

Keyword(s):

Mrna Expression ◽

Gonadal Hormones ◽

Female Rats ◽

Male Rats ◽

Mrna Levels ◽

Rat Stomach ◽

Adult Rats ◽

Stable Level ◽

Young Rats

OBJECTIVE: The recently isolated endogenous GH secretagogue, named ghrelin, is a gastric peptide of 28 amino acids with an n-octanoylation in the serine 3 that confers the biological activity to this factor. Ghrelin has been shown to directly stimulate GH release in vivo and in vitro and to be involved in the regulation of gastric acid secretion and motility. In the present work we have studied gender and gonadal dependency of ghrelin mRNA expression in rat stomach. DESIGN AND METHODS: We analysed ghrelin mRNA expression in rat stomach by Northern blot analysis. We also examined the effect of gonadal steroid deprivation on ghrelin mRNA expression. RESULTS AND CONCLUSIONS: The results obtained showed clearly that ghrelin gastric mRNA expression increased with age in young rats (up to 90 days old) but exhibited no significant sex difference at each age tested. Ghrelin mRNA levels were lowest at postnatal day 9, reaching a stable level of expression at day 40 in both female and male rats, although the increase in female rats appears much more gradual than that in males. Moreover, neither ovariectomy nor orchidectomy significantly modified ghrelin mRNA gastric levels in adult rats. In conclusion, these data indicate that ghrelin mRNA expression is associated with age and that a progressive increase is present from the perinatal period up to a stable level after puberty. Gonadal hormones did not alter ghrelin mRNA levels. Taken together, these data showed that ghrelin mRNA levels in young rats are age but not gender dependent, and are not influenced by gonadal steroids.

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Epigenetic Signatures of Early Life Adversities in Animal Models: A Role for Psychopathology Vulnerability

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.145 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S29-S29

Author(s):

M.A. Riva

Keyword(s):

Dna Methylation ◽

Prefrontal Cortex ◽

Female Rats ◽

Behavioral Alterations ◽

Bdnf Expression ◽

Adult Rats ◽

Major Mechanism ◽

Receptor Modulator ◽

Male And Female Rats ◽

Differentially Methylated Genes

Stressful experiences early in life (ELS) represent one of the most relevant factors for the vulnerability to psychopathologies. Epigenetic changes, such as DNA methylation, have emerged as a major mechanism through which ELS can alter adult behaviour leading to persistent changes of gene regulation.We performed DNA methylation analyses in the hippocampus and prefrontal cortex of adult rats exposed to stress during gestation (PNS), a model that is associated with persistent behavioral alterations relevant for psychiatric disorders.Using an epigenome-wide analysis, an overlap of 893 differentially methylated genes was observed between hippocampus and prefrontal cortex of adult male and female rats exposed to PNS. The list includes several genes previously associated with schizophrenia and other psychiatric conditions, such as calcium and potassium voltage operated channels as well as GABA and glutamate receptor subunits. By restricting the overlap to genes that were modulated in the same direction, we identified miR-30a as being less methylated in PNS rats. Interestingly one of the targets for this miRNA is the neurotrophin BDNF, whose expression was indeed reduced as a consequence of the prenatal manipulation. Interestingly chronic treatment of PNS rats with the multi-receptor modulator lurasidone during adolescence was able to prevent the changes in miR30a and BDNF expression.These results highlight the importance for the identification of methylation signatures through which stress exposure early in life could engrave on the outcome of the adult phenotype, and may allow the identification of novel genes and pathways that are affected as a consequence of ELS.Disclosure of interestM.A.R. has received compensation as speaker/consultant from Lundbeck, Otzuka, Sumitomo Dainippon Pharma and Sunovion. He has received research grants from Lundbeck, Sumitomo Dainippon Pharma and Sunovion.

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Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00441.2007 ◽

2008 ◽

Vol 104 (3) ◽

pp. 648-654 ◽

Cited By ~ 57

Author(s):

M. N. Horcajada ◽

V. Habauzit ◽

A. Trzeciakiewicz ◽

C. Morand ◽

A. Gil-Izquierdo ◽

...

Keyword(s):

Bone Loss ◽

Bone Mass ◽

Age Groups ◽

Female Rats ◽

Lipid Lowering ◽

Mineral Density ◽

Adult Rats ◽

Young Rats ◽

Ovx Rats ◽

Intact Rats

The main aim of this study was to investigate the bone-sparing effect of hesperidin, one of the main flavonoid present in oranges, in two age groups of ovariectomized female rats, compared with their intact controls. Young (3 mo) and adult (6 mo) female Wistar rats were sham operated (SH) or ovariectomized (OVX) and then pair-fed for 90 days a casein-based diet supplemented or not with 0.5% hesperidin (Hp; n = 10/group). In older rats, Hp intake led to a partial inhibition of OVX-induced bone loss, whereas a complete inhibition was obtained in younger animals. At both ages, while plasma osteocalcin concentrations were unchanged, urinary excretion of deoxypyridinoline was reduced by Hp intake, suggesting that Hp was able to slow down bone resorption. Unexpectedly, in intact young rats, Hp consumption resulted in a significant increase in bone mineral density (BMD). Indeed, 6-mo-old HpSH rats had a similar BMD to 9-mo-old nontreated SH adult rats, suggesting an accelerated bone mass gain in the young rats. In contrast, in intact adult rats, Hp did not further increase BMD but did improve their bone strength. The results of this study show a protective effect of Hp on bone loss in OVX rats of both ages without uterine stimulation and accompanied by a lipid-lowering effect. The unexpected and intriguing findings obtained in intact rats showing improved BMD in young rats and improved femoral load in adult rats merit further investigation. The bone and lipid benefits of hesperidin make it an attractive dietary agent for the management of the health of postmenopausal women.

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Hydrogen Sulfide Alleviates Anxiety, Motor, and Cognitive Dysfunctions in Rats with Maternal Hyperhomocysteinemia via Mitigation of Oxidative Stress

Biomolecules ◽

10.3390/biom10070995 ◽

2020 ◽

Vol 10 (7) ◽

pp. 995 ◽

Cited By ~ 3

Author(s):

Olga Yakovleva ◽

Ksenia Bogatova ◽

Renata Mukhtarova ◽

Aleksey Yakovlev ◽

Viktoria Shakhmatova ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Sulfide ◽

Motor Coordination ◽

Female Rats ◽

Fine Motor ◽

Control Group ◽

Behavioral Alterations ◽

Neuroprotective Effects ◽

Sodium Hydrosulfide ◽

Behavioral Impairments

Hydrogen sulfide (H2S) is endogenously produced from sulfur containing amino acids, including homocysteine and exerts neuroprotective effects. An increase of homocysteine during pregnancy impairs fetal growth and development of the offspring due to severe oxidative stress. We analyzed the effects of the H2S donor—sodium hydrosulfide (NaHS) administered to female rats with hyperhomocysteinemia (hHcy) on behavioral impairments and levels of oxidative stress of their offspring. Rats born from females fed with control or high methionine diet, with or without H2S donor injections were investigated. Rats with maternal hHcy exhibit increased levels of total locomotor activity and anxiety, decreased muscle endurance and motor coordination, abnormalities of fine motor control, as well as reduced spatial memory and learning. Oxidative stress in brain tissues measured by activity of glutathione peroxidases and the level of malondialdehyde was higher in rats with maternal hHcy. Concentrations of H2S and the activity and expression of the H2S generating enzyme—cystathionine-beta synthase—were lower compared to the control group. Administration of the H2S donor to females with hHcy during pregnancy prevented behavioral alterations and oxidative stress of their offspring. The acquisition of behavioral together with biochemical studies will add to our knowledge about homocysteine neurotoxicity and proposes H2S as a potential agent for therapy of hHcy associated disorders.

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Physical exercise protects dynamic balance and motor coordination of rats treated with vincristine

Revista Brasileira de Fisiologia do Exercício ◽

10.33233/rbfex.v19i5.4220 ◽

2020 ◽

Vol 19 (5) ◽

pp. 336

Author(s):

Luiza Minato Sagrillo ◽

Viviane Nogueira De Zorzi ◽

Luiz Fernando Freire Royes ◽

Michele Rechia Fighera ◽

Beatriz Da Silva Rosa Bonadiman ◽

...

Keyword(s):

Oxidative Stress ◽

Locomotor Activity ◽

Physical Exercise ◽

Motor Coordination ◽

Dynamic Balance ◽

Exercise Group ◽

Adult Rats ◽

The Central Nervous System ◽

Stress Damage ◽

Training Protocol

Physical exercise has been shown to be an important modulator of the antioxidant system and neuroprotective in several diseases and treatments that affect the central nervous system. In this sense, the present study aimed to evaluate the effect of physical exercise in dynamic balance, motor coordination, exploratory locomotor activity and in the oxidative and immunological balance of rats treated with vincristine (VCR). For that, 40 adult rats were divided into two groups: exercise group (6 weeks of swimming, 1h/day, 5 days/week, with overload of 5% of body weight) and sedentary group. After training, rats were treated with 0.5 mg/kg of vincristine sulfate for two weeks or with the same dose of 0.9% NaCl. The behavioral tests were conducted 1 and 7 days after each dose of VCR. On day 15 we carried out the biochemical analyzes of the cerebellum. The physical exercise was able to protect against the loss of dynamic balance and motor coordination and, had effect per se in the exploratory locomotor activity, and neutralize oxidative stress, damage DNA and immune damage caused by VCR up to 15 days after the end of the training protocol. In conclusion, we observed that previous physical training protects of the damage motor induced by vincristine.Key-words: exercise, oxidative stress, neuroprotection, cerebellum.

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INDUCTION OF GOITRE BY PTU OR KClO4 IN MALE AND FEMALE RATS. EFFECT OF GONADECTOMY

Acta Endocrinologica ◽

10.1530/acta.0.0740088 ◽

1973 ◽

Vol 74 (1) ◽

pp. 88-104 ◽

Cited By ~ 2

Author(s):

T. Jolín ◽

M. J. Tarin ◽

M. D. Garcia

Keyword(s):

Iodine Content ◽

High Plasma ◽

Disc Electrophoresis ◽

Female Rats ◽

Male Rats ◽

Adult Rats ◽

Male And Female ◽

Glucose Levels ◽

Male And Female Rats ◽

Tsh Levels

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.

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PHYSIOLOGICAL EFFECTS OF THE PINEAL GLAND IN ANDROGEN-STERILIZED FEMALE RATS

Acta Endocrinologica ◽

10.1530/acta.0.0630667 ◽

1970 ◽

Vol 63 (4) ◽

pp. 667-678 ◽

Cited By ~ 4

Author(s):

Russel J. Reiter

Keyword(s):

Pineal Gland ◽

Reproductive Organs ◽

Female Rats ◽

Inhibitory Influence ◽

Light Deprivation ◽

Vaginal Smears ◽

Adult Rats ◽

Androgen Treatment ◽

Postnatal Treatment ◽

Cervical Ganglia

ABSTRACT The influence of early androgen treatment, light deprivation (by blinding), pinealectomy and superior cervical ganglionectomy on the reproductive system of female rats was tested. Early postnatal treatment of rats with testosterone propionate caused adult rats to exhibit the characteristic signs of androgen sterilization; these included polyfollicular ovaries, normal-sized uteri and persistent vaginal cornification. If early androgentreated rats also were blinded the ovaries were smaller in size and contained fewer follicles, the uteri were greatly reduced in size and the incidence of vaginal oestrus was decreased by approximately 50% If in addition to blinding, androgen-sterilized animals were subjected to either removal of the pineal gland or superior cervical ganglia, the reproductive organs and the vaginal smears were indistinguishable from those of testosterone-treated rats with eyes. These data indicate that the inhibitory influence of blinding on the pituitary-ovarian axis was mediated through the sympathetic nervous system and the pineal gland. The restraining influence of light deprivation on the growth of the reproductive organs was not permanent as illustrated by the fact that if these animals were kept to 120 days of age the ovaries and uteri grew to the same level as those of pinealectomized control rats.

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Developmental study of benzodiazepine effects on monosynaptic GABAA-mediated IPSPs of rat hippocampal neurons

Journal of Neurophysiology ◽

10.1152/jn.1993.70.3.1076 ◽

1993 ◽

Vol 70 (3) ◽

pp. 1076-1085 ◽

Cited By ~ 37

Author(s):

C. Rovira ◽

Y. Ben-Ari

Keyword(s):

Hippocampal Neurons ◽

Receptor Agonist ◽

Hippocampal Slices ◽

Pyramidal Cells ◽

Developmental Study ◽

Type I ◽

Gamma Aminobutyric Acid ◽

Adult Rats ◽

Young Rats ◽

In Cells

1. The effects of type I (BZ1) and type II (BZ2) benzodiazepine receptor ligands on monosynaptic gamma-aminobutyric acid (GABA)A-mediated inhibitory postsynaptic potentials (IPSPs) and on responses to exogenously applied GABA were studied using intracellular recordings from CA3 pyramidal cells of rat hippocampal slices taken at different postnatal stages [postnatal day 4 (P4)-P35)]. 2. The effects of midazolam, a BZ1 and BZ2 receptor agonist, were tested on the monosynaptic IPSPs at different stages. Monosynaptic, bicuculline-sensitive IPSPs were evoked by hilar stimulation in presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) antagonists [6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and D(-)2-amino-5-phosphonopentanoic acid (50 microM)]. Midazolam at 300 nM maximally increased the duration and amplitude of monosynaptic GABAA-mediated IPSPs in neurons from pups (P4-P6, n = 6) and young (P7-P12, n = 8) and adult (P25-P35, n = 9) rats. All the effects of midazolam on IPSPs were reversed by the antagonist Ro 15-1788 (10 microM). 3. The effect of midazolam was also tested on the response to exogenously applied GABA (5 mM) in the presence of tetrodotoxine [TTX (1 microM)]. In neurons from young rats (n = 9), midazolam (1 nM-1 microM) did not change the responses to exogenously applied GABA, whereas in adult rats (n = 8) midazolam maximally increased GABA currents at 30 nM. 4. The effect of zolpidem, a BZ1 receptor agonist, was tested on monosynaptic IPSPs and GABA currents at different stages. Zolpidem (10 nM-1 microM) was inactive in cells from young rats (n = 12). In neurons from adult rats, zolpidem maximally increased the duration and amplitude of the monosynaptic IPSPs at 300 nM (n = 5) and the amplitude of GABA current at 30-100 nM (n = 5). 5. Methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) (300 nM), an inverse agonist of BZ1 and BZ2 receptors, decreased the amplitude and duration of monosynaptic IPSPs in neurons from pups (n = 3) and young (n = 4) and adult (n = 5) rats. In all cases, full recovery was obtained after exposure to R0 15-1788 (10 microM). DMCM (300 nM-10 microM) failed to reduce GABA responses in cells from young (n = 3) or adult (n = 7) rats. 6. Results indicate that the regulation by benzodiazepine of GABAA-mediated IPSPs varies with the developmental stage.(ABSTRACT TRUNCATED AT 400 WORDS)

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