scholarly journals Total DNA methylation in the brain in response to decitabine treatment in female rats

2019 ◽  
Vol 66 (1) ◽  
pp. 1-3
Author(s):  
L. Balagova ◽  
K. Buzgoova ◽  
P. Karailiev ◽  
D. Jezova
Keyword(s):  
Dna Methylation ◽  
Anticancer Drugs ◽  
Brain Regions ◽  
Female Rats ◽  
Male Rats ◽  
Antidepressant Effects ◽  
Total Dna ◽  
Aberrant Dna Methylation ◽  
The Brain ◽  
Scarce Data

Abstract Hypomethylating agent decitabine is being used in the treatment of certain types of leukaemia in combination with other anticancer drugs. Aberrant DNA methylation has been suggested to occur in pathological states including depression. Scarce data in male rats suggest antidepressant effects of decitabine. The main aim of our studies is to test the hypothesis that the inhibition of DNA methylation results in antidepressant effects in female rats. Before doing so, we decided to verify the effects of decitabine on DNA methylation in females. The findings demonstrate that the treatment with decitabine at the dose shown previously to inhibit DNA methylation in males, had no effect on total DNA methylation in two brain regions, namely the hippocampus and frontal cortex of female rats. In conclusion, the present study allows us to suggest that the effect of decitabine on DNA methylation in the brain is sex dependent.

scholarly journals Local Cerebral Glucose Utilization in Normal Female Rats: Variations during the Estrous Cycle and Comparison with Males

1985 ◽  
Vol 5 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Alison M. Crane ◽  
Louis Sokoloff
Keyword(s):  
Estrous Cycle ◽  
Glucose Utilization ◽  
Brain Regions ◽  
Female Rats ◽  
Male Rats ◽  
Normal Male ◽  
Normal Female ◽  
Female Rat ◽  
Males And Females ◽  
The Brain

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.

scholarly journals Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nicole M. Wanner ◽  
Mathia Colwell ◽  
Chelsea Drown ◽  
Christopher Faulk
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Coat Color ◽  
Brain Regions ◽  
Functional Enrichment ◽  
Positive Effects ◽  
Genome Wide ◽  
Nulliparous Female ◽  
The Impact ◽  
The Brain

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively. Results F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms. Conclusions These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.

scholarly journals Effects of early neonatal proinflammatory stress on the expression of BDNF transcripts in the brain regions of prepubertal male rats

2016 ◽  
Vol 20 (2) ◽  
pp. 191-197
Author(s):  
D. I. Peregud ◽  
S. V. Freiman ◽  
A. O. Tishkina ◽  
L. S. Sokhranyaeva ◽  
N. A. Lazareva ◽  
...  
Keyword(s):  
Brain Regions ◽  
Male Rats ◽  
The Brain

Effects of early neonatal proinflammatory stress on the expression of BDNF transcripts in the brain regions of prepubertal male rats

2017 ◽  
Vol 7 (1) ◽  
pp. 121-127 ◽  
Author(s):  
D. I. Peregud ◽  
S. V. Freiman ◽  
A. O. Tishkina ◽  
L. S. Sokhranyaeva ◽  
N. A. Lazareva ◽  
...  
Keyword(s):  
Brain Regions ◽  
Male Rats ◽  
The Brain

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

scholarly journals The Effect of Gender on Brain Tissue Changes Induced by Renal Ischemia-Reperfusion Injury in Adult Rats

2019 ◽  
Vol 8 (2) ◽  
pp. 113-118
Author(s):  
Fakhri Armin ◽  
Fariba Azarkish ◽  
Ali Atash Ab Parvar ◽  
Aghdas Dehghani
Keyword(s):  
Brain Tissue ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Renal Ischemia ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Sensitive Organ ◽  
The Brain

Background: Renal ischemia-reperfusion (RIR) is a common clinical injury that affects the function of other remote organs such as the brain by initiating a cascade of complex and wide-ranging inflammatory responses. RIR also follows a different course in men and women. Since there is little information on the effect of RIR on the brain as a sensitive organ in both males and females, the present research was performed to investigate the effect of gender on RIR-induced brain tissue alterations in adult rats. Materials and Methods: In this study, 28 Wistar rats (14 female and 14 male rats) weighing 200 ± 20 g were divided into the following groups: 1- male sham (MS), 2- female sham (FS), 3- male ischemia (MI) with 3-hour reperfusion (ISC3hr), and 4- Female ischemia (FI) with 3-hour reperfusion (ISC3hr). Bilateral renal ischemia was induced for 45 minutes and blood samples were taken after reperfusion for the measurements of serum blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitrite levels. The left kidney was removed for evaluation of MDA and tissue nitrite levels. Right kidney and brain tissue underwent histological examination. Results: Serum BUN level increased in both genders. Serum nitrite level was significantly different between both genders, meaning that it was increased in the female rats as compared to male ones. Overall brain tissue damage was significantly increased in males compared to females. Conclusion: RIR has an effect on the function and tissue of kidney and brain in both genders. Female rats are more susceptible to the nitric oxide system than the male ones. This study showed that male brain tissue was more susceptible to RIR. Therefore, gender is one of the important factors that should be considered in clinical treatments.

scholarly journals Sex Differences in the Brain-Blood Barrier in Rats Exposed to Early life Stress and the Treatment with Antidepressants and Psychobiotic

2021 ◽  
Author(s):  
Maria Eduarda M. Botelho ◽  
Anelise S. Carlessi ◽  
Luana M. Manosso ◽  
Laura A. Borba ◽  
Airam B. de Moura ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Life Stress ◽  
Early Life Stress ◽  
Maternal Deprivation ◽  
Female Rats ◽  
Male Rats ◽  
Major Depressive ◽  
Male And Female Rats ◽  
The Brain ◽  
Age And Sex

Abstract Major depressive disorder is a debilitating mental disorder. Although the etiology is not fully understood, the impairment to the blood-brain barrier (BBB) integrity may be involved. Maternal deprivation was performed in the first 10 postnatal days for 3h/day. Male and female rats were divided into control and maternal deprivation. Maternal deprivation animals were subdivided and received treatment with saline, escitalopram, ketamine, or probiotic. The integrity of BBB was evaluated in the prefrontal cortex and hippocampus at postnatal days 11, 21, 41, and 61. Maternal deprivation caused BBB breakdown in the prefrontal cortex and hippocampus in female and male rats in all ages evaluated, except in the prefrontal cortex of females at postnatal day 41. In females, escitalopram, ketamine, and probiotic reversed BBB breakdown in all ages evaluated, except probiotic at postnatal day 21 (prefrontal cortex), and ketamine at postnatal days 21 and 41 (hippocampus). In males, escitalopram, ketamine, and probiotic reversed BBB breakdown in the prefrontal cortex in all ages evaluated, except escitalopram at postnatal days 41 and 61. In the hippocampus of males, BBB damage was reversed by escitalopram at postnatal day 21 and ketamine at postnatal day 41. Treatment with escitalopram, ketamine, or probiotics can prevent changes in the BBB integrity, depending on the age and sex of the animal. Clinically it is important to evaluate different treatments depending on age and sex.

Effects of thiopental anesthesia on local rates of cerebral protein synthesis in rats

1998 ◽  
Vol 274 (5) ◽  
pp. E852-E859
Author(s):  
C. Beebe Smith ◽  
C. Eintrei ◽  
J. Kang ◽  
Y. Sun
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Statistical Significance ◽  
Brain Regions ◽  
Male Rats ◽  
Protein Breakdown ◽  
Relative Contribution ◽  
Anesthetized Rats ◽  
Cerebral Protein Synthesis ◽  
The Brain

We have examined the effects of a surgical level of thiopental anesthesia in adult male rats on local rates of cerebral protein synthesis with the quantitative autoradiographicl-[1-14C]leucine method. The relative contribution of leucine derived from protein breakdown to the intracellular precursor amino acid pool for protein synthesis was found to be statistically significantly decreased in the anesthetized rats compared with controls. In the brain as a whole and in 30 of the 35 brain regions examined, rates of protein synthesis were decreased (1–11%) in the anesthetized rats. Decreases were statistically significant ( P ≤ 0.05) in the brain as a whole and in six of the regions, and they approached statistical significance in an additional 13 regions, indicating a tendency for a generalized but small effect.

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