homayoun khazali

Formononetin is a flavonoid compound derived from various plants, such as red clover. Calcitonin gene-related peptide (CGRP) and Orexin are among the important neuropeptides in the hypothalamus in controlling stress responses. Moreover, previous studies have indicated the anti-stress effects of formononetin. However, its molecular mechanism has not yet been elucidated. The present study aimed to evaluate the effect of formononetin on the hypothalamic expression of CGRP and HCRT (the hypocretin neuropeptide precursor) in a rat model of stress.

In this experimental study, 20 male Wistar rats weighing 200±10 g were divided into four groups (n=5 for each group). For stress induction, rats were placed in a restraint cage for 2 h. Formonontin with 20 µg and 40 μg doses was injected in a single dose with a volume of 3 μl via the third cerebral ventricle. Then, the hypothalamic samples were removed, and real-time polymerase chain reaction (RT-PCR) was performed to measure gene expression.

In the stress rat model, the expression of CGRP and HCRT genes significantly decreased compared to the control group (P≤0.01). The injection of formononetin significantly decreased the expression of CGRP and HCRT genes compared to stress model rats (P≤0.01).

The present study indicated the anti-anxiety effects of formononetin. The anxiolytic effects of formononetin may be exerted by down-regulating the function of the stress-related neurons in the hypothalamus.

Chrysin is a natural flavonoid with several demonstrated neuro-pharmacological effects in brain areas related to anxiety. However, the intra-hypothalamic molecular mechanisms underlying the anxiolytic effects of chrysin remain unclear.

The current study revealed the effects of chrysin on hypothalamic corticotrophin-releasing hormone ( CRH ) and calcitonin gene-related peptide ( CGRP ) gene expression levels in a rat model of stress.

Thirty male Wistar rats weighing 200 ± 10 g were divided into six groups for this investigation. Acute restraint stress was induced in the animals for 2 hours. Intact or stress-induced rats received 20 or 40 µg of chrysin via the third cerebral ventricle, respectively. Open-field and forced swimming tests were performed to evaluate stress-related behaviors. Hypothalamic samples were then removed, and real-time polymerase chain reaction (PCR) was used to measure relative gene expression.

The results showed that in the rats receiving chrysin, CRH and CGRP gene expression levels were significantly decreased compared to the stress group. Additionally, chrysin injection reduced anxiogenic behaviors.

Chrysin decreased the expression of hypothalamic CRH and CGRP genes in stressed rats.

In healthy people, dopamine stimulates ghrelin secretion. The level of dopamine release  and ghrelin is lower in the patients with polycystic ovary syndrome (PCOS). In the present study,we investigated the effects of doplamin and L-dopa on relative gene expression of ghrelin in PCOS model rats.

In the first step of the study, PCOS was induced in 25 female Wistar rat (Rattus norvegicus) by injection of estradiol. Then, the rats received saline, dopamine (5µg), L-dopa (5µg) or simultaneous injections of sulpride (10µg/kg), SCH23390 hydrochloride (10µg/kg) and dopamine or L-dopa respectively via third cerebral ventricular. In the second part of the study, 15 PCOS rats received saline L-dopa (100mg/kg) or dopamine (50mg/kg) intraperitoneally. Hypothalamic and ovarian samples were dissected. Mean relative ghrelin gene expression was determined by real- time-PCR method. 

Mean relative gene expression of ghrelin significantly decreased in the hypothalamus and ovary of the rats with PCOS compared to those in the intact rats. Intraventricular injection of dopamine or L-dopa significantly increased the hypothalamic ghrelin gene expression in comparison to that in the rats in the PCOS group. Dopamine or L-dopa did not significantly increase the gene expression of ovarian ghrelin in comparison to that in PCOS group. Injections of sulpride and SCH23390 significantly blocked the stimulatory effects of dopamine or L-dopa on the ghrelin gene expression in hypothalamus compared to those in the dopamine or L-dopa group.

The dopaminergic pathway may be involved in increasing ghrelin gene expresion extremely via hypothamic level in PCOS condition.

It is well established that ghrelinerghic system has an inhibitory effect on reproductive activity. RFamide-related peptide-3 (RFRP-3) is one of the most important neuropeptides that regulates the mammalian reproduction. Studies have indicated the presence of the ghrelin receptor, called the growth hormone secretagogue receptor (GHS-R1a), in the RFRP-3 containing areas in the brain. Thus, it may be possible that ghrelinergic system involves in the control of reproduction through the RFRP-3. The aim of this study was to investigate the possible role of the GHS-R1a receptors in the regulation of RFRP-3 and its receptor GPR147 mRNA expression in the hypothalamus of male rats.

40 male Wistar rats in were divided in 8 groups (n=5) and each group received saline, 2,-4 or-8nmol ghrelin, 5,-10 or-20nmol D-Lys3-GHRP-6 (DLS), or concomitantly of ghrelin (4nmol) and DLS (10nmol) via the stereotaxically implanted cannula. Hypothalamus of rats was dissected 2h after treatment for evaluation of RFRP-3 and GPR147 mRNA levels.

Our findings indicated that 4nmol (P<0.05) or 8nmol (P<0.01) ghrelin injection significantly increased the RFRP-3 mRNA expression compare to saline group. While, the injection of 20nmol DLS significantly (P<0.05) decreased the RFRP-3-mRNA level when compared to saline group. Pretreatment of ghrelin-received animals with DLS prevented the increasing effects of ghrelin on RFRP-3 gene expression. Ghrelin or DLS had no significant effects on hypothalamic GPR147-mRNA levels.

The acute activation of GHS-R1a by gherlin has a stimulatory role in hypothalamic RFRP-3 gene expression without any significant effects on GPR147-mRNA level in an acute treatment.

Chrysin is a bioactive component of herbal medicines such as Passiflora incarnate, Passiflora caerulea, and Oroxylum indicum. Although evidence has demonstrated the neuroprotective, anti-inflammatory, and pain-relieving effects of chrysin, the intra-hypothalamic molecular mechanisms underlying the anxiolytic effects of chrysin are still unclear. This study aimed to explore the effects of chrysin on hypothalamic orexin and melanin-concentrating hormone (MCH) gene expression in a rat model of stress.

Twenty male Wistar rats (200 ± 10 g) were segregated into four groups (n = 5). For the induction of stress, the animals were placed in the restraint cage for 2 hours. The intact and stressed groups received saline. Thirty minutes before the induction of stress, chrysin was injected into the other two groups of the stress model at a dosage of 20 or 40 μg via the third cerebral ventricle. Hypothalamic samples were removed and frozen, and the relative gene expression of orexin and MCH was measured using the real-time polymerase chain reaction technique.

The induction of stress significantly increased mRNA levels of orexin and MCH compared to the control rats. The mRNA levels of MCH and orexin significantly declined in rats receiving chrysin compared to the stress group.

The inhibition of the hypothalamic MCH and orexin neuronal circuits may be involved in the preventive effects of chrysin against stressful situations. Chrysin may be a potential target to manage anxiogenic behaviors due to the down-regulation of MCH and orexin gene expression upstream the hypothalamic corticotropin-releasing hormone.

The aim of the research was to block orexin receptors in the hippocampus and investigate the changes in passive avoidance memory, motor coordination and balance in the absence of orexin effects. The effect of intra-hippocampal injection of the orexin receptor type 2 antagonist JNJ-10397049 on passive avoidance memory, motor coordination and balance was not investigated in previous studies, which we addressed in this research.

Twenty adult male Wistar rats weighing 220-250 grams were randomly divided into four groups. Animals in each group respectively received saline, Orexin A, Orexin A and Orexin receptor type 1 antagonist, or Orexin A and Orexin receptor type 2 antagonist in their hippocampus. Subsequently, passive avoidance memory was evaluated using a shuttle box, while motor coordination and balance were assessed utilizing rotarod devices.

The average delay in entering the dark area and the total time that the animals spent in the light area of the shuttle box increased in the orexin-receiving group compared to the control group. However, these values significantly decreased in the groups that received both orexin and orexin receptor antagonists, in comparison to the group that received orexin alone (p < 0.01).
Furthermore, the duration of motor coordination and balance impairment 30 minutes after injection increased in the orexin-treated group compared to the control group, but it showed a significant decrease (p < 0.01) in the groups that received both orexin and orexin receptor antagonists, when compared to the group that received orexin alone.

It seems that orexin in the hippocampus improves the retrieval of passive avoidance memory, motor coordination and balance. On the other hand, Orexin receptor antagonists disrupt these two processes.
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Stress is defined as a physiological response to environmental conditions which could cause changes in the level of neuropeptides in the central nervous system. Trans- anethole is the secondary active compound with anti-stress and antioxidant properties. This research investigates the effects of trans-anethole on the hypothalamic CRH and CGRP gene expression in stress model rats.

Twenty male rats weighing 200-220 g were used. Animals were divided into four groups (n=5). The intact control or stress groups received saline. Two stress groups received trans-anethole (150 mg/kg or 250 mg/kg, IP). Thirty minutes following the injection of drugs, animals were subjected to acute immobilization stress for two hours. Then, behavioral tests were performed. The hypothalamic samples were removed. CRH and CGRP gene expression was measured using RT-PCR.

The mRNA levels of CGRP and CRH significantly increased in the stress group compared to those of the control. In rats receiving 150 mg/kg or 250 mg/kg of trans-anethole, the mRNA level of CGRP and CRH decreased significantly compared to that of the stress group. Also, injection of 150 mg/kg or 250 mg/kg of trans-anethole significantly improved the stressful behaviors compared to what happened in the stress group.

Trans-anethole may be considered as a potential anti-stress factor due to its inhibitory effects on the activity of hypothalamic stress pathways such as CRH and CGRP

Prolactin is a necessary factor for lactation and synthesis of milk constituent. Progesterone (P4) and 17β-estradiol (E2) are inhibitory factors for lactation. Orexin is involved in regulating the metabolism and lipid synthesis. Present study investigated the orexin B receptor antagonist and steroid hormone effects on milk lactose synthesis. Thirty Wistar lactating rats were used. Lactating animals in the group 1-4 received saline, 1, 2 or 4 µg of orexin antagonist. Lactating animals of the groups 5 and 6 received 4 µg of orexin antagonist plus 1 µg of 17-β estradiol (E2) or 4 mg of progesterone (p4). Blood and tissue samples were collected at 60 and 180 minutes of injections. Blood samples were measured for prolactin concentrations and tissue samples were examined for alpha lactalbumin (Lalba) and beta-1,4-galactosyltransferase 1 (B4galt1) gene expression in the mammary gland by RT-PCR technique. Injection of orexin antagonist significantly increased the percentage of milk lactose, plasma prolactin and Lalba gene expression in comparison to control group. Injections of E2 or P4 inhibited the increased effects of orexin antagonist on mean milk lactose percentage, prolactin and Lalba gene expression in comparison to orexin antagonist group. Injections of all drugs did not alter the mean B4galt1 gene expression. Stimulatory effects of orexin antagonist on milk production may be partly due to the increased prolactin concentration and Lalba gene expression. The mechanism by which the steroid hormones supress the orexin antagonist-induced lactose synthesis may be mediated partly via inhibiting the prolactin production.

Trans-anethole is a steroidogenic plant derivative. Adiponectin secretion and dopamine release is lower in patients suffer from polycystic ovary syndrome (PCOS). In the present study the effects of interaction of trans-anethole and L-dopa were investigated on serum concentration of adiponectin in PCOS model rats. Following estradiol valerate- induced PCOS, forty-five PCOS rats in 9 groups received saline, trans-anethole (50 mg/kg), L-dopa (100 mg/kg), sulpride (10 mg/kg), SCH23390 hydrochloride (1 mg/kg) or simultaneous injections of these drugs via intraperitoneal injection. Five intact rats received saline. Blood samples were collected via tail vein. Serum concentration of adiponectin was determined by ELISA. Mean serum concentration of adiponectin significantly decreased in PCOs rats compared to intact group. Adiponectin concentration in PCOS rats receiving trans- anethole or L-dopa significantly increased compared to PCOS group. Simultaneous injections SCH23390 hydrochloride and sulpride inhibit the stimulatory effects of L-dopa on serum concentration of adiponectin via exerting synergistic effects. Simultaneous injections of trans- anethole and L-dopa synergistically caused a significant increase in serum concentration of adiponectin compared to PCOS group. Trans-anethole as a steroidogenic plant derivative, may be an effective agent for increasing the activity of dopaminergic neurons and controlling the metabolic complication derived of decreased levels of adiponectin secretion in PCOS.

Although previous studies have demonstrated the importance of the orexin system in regulating enzymes involved in lipogenesis, its exact mechanism and the extent of this effect on different enzymes have remained unexplored. In this regard, this study is aimed at investigating the intra-duct injection of orexin receptor 1 and 2 antagonists (OX1RA and OX2RA) into the mammary glands. More specifically, the study probes the effect of this injection on glycerol 3-phosphate acyl transferase (Gpat1 and Gpat4) genes as well as the milk's triacylglycerol (TAG) level in lactating Wistar rats. Twenty four lactating Wistar rats were randomly divided into different experimental groups including the control group, the group receiving OX1RA and OX2RA intraductally (at doses of 5, 10, and 20 µg/kg of B.W.). Six hours after injection, the collection of milk samples were done using rat milking device, and TAG measurements were carried out. Moreover, using real time PCR, we measured target genes by a specific primer for each gene. One-way ANOVA with Tukey’s post hoc tests were used to analyze the results and the level of significance was considered P<0.05. The findings of the present study showed that the injection of orexin antagonists at a dose of 10 μg/kg resulted in a significant reduction in Gpat1 and Gpat4 gene expressions. In addition, the injection of antagonists with the same dose caused a significant decrease in TAG levels. Intra-ductal injection of orexin antagonists into the mammary gland decreases milk TAG levels and decreases the expression of Gpat1 and Gpat4 genes.

Polycystic Ovary Syndrome is one of the common endocrine disorders in women caused by an increase in testosterone. Aromatase enzyme decreases testosterone. In the present study, the effect of drug Pramipexol as dopamine agonist in three doses and two different times on ovarian aromatase gene expression in Wistar PCOS rats was investigated.

Thirty mice were divided to two groups (n = 15) including three subgroups of solvent, PCOS (injection of 2 mg of Estradiol valerate), and PCOS + drug (1, 2, 4 mg/kg). Pramipexol was administered 15 or 30 days after induction of PCOS, as group 1 or 2, for 14 days. Aromatase gene expression was then measured, and analyzed by One-way ANOVA analysis of variance and Tukey's post hoc test.

The results showed an increase in aromatase gene expression in the subgroups receiving the drug (p < 0.05, p < 0.01, p < 0.001) in each of the two study groups. There was significant difference between 2 groups in gene expression after drug treatment by 2, and 4 mg/kg (p < 0.01, p < 0.05).

Pramipexol doses 1, 2, 4 mg/kg increased the expression of the ovarian aromatase gene in PCOS mice in a time and dose-dependent manner. Pramipexol 4 mg/kg, 15 days after induction of PCOS caused the greatest increase in aromatase gene expression and can be suggested to improve PCOS.
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Thymoquinone stimulates the activity of hypothalamic-pituitary-gonadal axis (HPG). Diabetes, ghrelin and aromatase are associated with decreased function of HPG axis. This study aimed to investigate the influence of thymoquinone on aromatase and ghrelin gene expression in intact and diabetic rats.
Twenty male Wistar rats weighing 190-220 g were used. Diabetes type 1 was induced by alloxan. Saline or thymoquinone (10 mg/kg) was injected into intact or diabetic rats intraperitoneally for two weeks. One day after last injection, the hypothalamic samples were removed. Relative gene expression of aromatase and ghrelin was determined by RT-PCR method.
Thymoquinone did not alter the aromatase expressions in the healthy rats. However, it caused a marked decrease in ghrelin expression in healthy rats. The aromatase and ghrelin expression significantly reduced in the diabetic rats receiving thymoquinone in comparison with diabetic group.
Thymoquinone may be a drug to improve decreased HPG axis activity of diabetic rats due to its inhibitory effects on aromatase and ghrelin upstream GnRH neurons.

5-Hydroxytryptamine (5HT) and kisspeptin are satiety factors, and ghrelin and adiponectin are orexigenic peptides. In this study, the mediating role of 5HT in the effects of GPR54 receptor blocking on ghrelin and adiponectin secretion was investigated.

Male Wistar rats weighing 220-250 g received saline, kisspeptin 10 (1 or 3 nmol), 5HT (2, 5 or 10 µg), kisspeptin plus 5HT, or peptide 234 (P234) plus 5HT via the third cerebral ventricle. Serum ghrelin and adiponectin concentrations were determined using the enzymelinked immunosorbent assay method.

Kisspeptin or 5HT treatment significantly reduced serum concentrations of ghrelin and adiponectin in comparison with saline. The injection of 2 nmol of P234+5HT significantly reduced serum ghrelin concentration compared to the 5HT alone, kisspeptin alone, and kisspeptin+5HT groups. Injections of either 1 or 2 nmol of P234 along with 5HT significantly declined the mean serum adiponectin level compared to rats received the kisspeptin plus 5HT.

Kisspeptin/GPR54 signaling pathway may be a putative target in serotonergic neurons to control ghrelin and adiponectin secretion.

Orexins regulate the body's energy balance during lactation. Also, Orexin A has been reported to have lipogenic effects on adipose tissue, but its role in the mammary glands is unclear. Acetyl CoA carboxylase (ACC) and glucose 6-phosphate dehydrogenase (G6PD) is critical lipogenic enzymes that catalyze the rate-limiting steps in milk fatty acid synthesis. This study was performed for the first time to investigate the effects of blocking the function of orexin-A in lactating female rats on the gene expression of mammary lipogenic enzymes and possible interaction with serum insulin hormone.

Orexin A receptor antagonist (SB-334867-A) was injected at three doses of 1, 2, and 4 μg/kg BW, in a volume of 50 μl solvent by intra-ductal method into the mammary glands of lactating rats and breast tissues were taken after eight hours. Serum insulin levels using ELISA and the relative expression of mammary ACC and G6PD were measured.

Quantitative PCR results showed that by injecting 4 μg/kg BW of SB intra-ductally, a parallel decrease in the gene expression of ACC and G6PD and serum insulin levels was observed compared with the control group.

Blocking the function of orexin-A in the lactating rats decreased the expression of lipogenic mammary enzymes and serum insulin.

Orexin A and adiponectin are involved in controlling metabolism and energy distribution in the body during lactation. Lactation is a process with high demand for lipid synthesis. Peroxisome proliferator-activated receptor gamma (PPARγ) and sterol regulatory element-binding protein 1 (SREBP1c) are two transcription factors that regulate milk lipid synthesis. The goal of this study was to assess the effects of mammary administration of the orexin A receptor antagonist on the expression of PPARγ and SREBP1c genes as well as serum adiponectin levels in the lactating rats.

Orexin A receptor antagonist (SB-334867) was injected intraductal into the mammary glands of lactating female rats at three doses of 1, 2 and 4 μg/kg BW in a solvent volume of 50 μL. The gene expressions of PPARγ and SREBP1c were measured using real-time polymerase chain reaction (PCR), along with serum levels of adiponectin using ELISA.

The results of quantitative RT-PCR showed a significant decrease in the relative expression of PPARγ and SREBP1c genes compared to that of the control group. The rate of reduction at a dose of 4 µg/kg BW SB was greater than the doses of 1 and 2 µg/kg BW SB-334867. The serum levels of adiponectin significantly decreased in the 4 µg/kg BW SB group compared to that of the control group.

These results indicated that intra-mammary administration of 4 µg/kg orexin-A antagonist in lactating rats decreased the gene expression of two transcription factors involved in milk fat synthesis, accompanying by a reduction in serum adiponectin level.

Kisspeptin is a hypothalamic peptide which stimulates hypothalamus- pituitary- gonadal (HPG) axis. Morphine is an alkaloid which suppresses reproduction. Ghrelin and leptin are metabolic peptides which play role in relaying information to the HPG axis. In the present study, the interaction effects of kisspeptin and morphine were investigated on plasma and gene expression levels of leptin and ghrelin. Twenty adult male Wistar rats in four groups received injection of saline, kisspeptin (1nmol), morphine (5mg kg-1) or kisspeptin+ morphine. Rats received kisspeptin and morphine via third cerebral ventricular and subcutaneous injection respectively. Ten male rats in two groups received intravenous injection of saline or kisspeptin (7/5nmol). Blood samples, hypothalamic and adipose tissue samples were collected. Plasma and gene expression levels of ghrelin and leptin were measured by using the methods of enzyme-linked immunosorbent assay and real time-PCR respectively. Morphine significantly increased plasma concentration and hypothalamic mRNA levels of ghrelin compared to saline while kisspeptin significantly decreased them compared to saline. Morphine significantly decreased plasma and mRNA levels of leptin in adipose tissue compared to saline but kisspeptin did not increase plasma and mRNA levels of leptin in adipose tissue compared to saline. Kisspeptin significantly decreased the effects of morphine on plasma concentration and hypothalamic gene expression levels of ghrelin compared to alone morphine but it did not affect morphine’s influence on plasma and leptin gene expression levels compared to alone morphine. Kisspeptin and morphine may be involved in the regulation of reproductive activity partly via regulation the metabolic hormones synthesis.

Memory-dependent psychological behaviors have an important role in life. Memory strengthening in adulthood to prevent its defects in aging is a significant issue. The ghrelin endogenous hormone improves memory by targeting glutamatergic and serotonergic circuits. Also, citicoline, a memory strengthening drug in aging, is not recommended to adults due to its side effects. The current study aims to test that ghrelin treatment, like citicoline, would improve passive avoidance memory via expression of the genes encoding the N-methyl-D-aspartate receptor (NMDAR1) and the serotonin receptor 1A (HTR1a) involved in this process.

Five groups of adult male rats received (1) saline (as control), (2) 0.5 mg/kg citicoline, or (3-5) 0.3, 1.5, and 3 nmol/μl ghrelin). The rats received the drugs via intra-hippocampal injection. Passive avoidance memory was determined using a shuttle box device. The latency to enter the dark chamber before (IL) and after (RL) injection and the total duration of the animal's presence in the light compartment (TLC) were evaluated. Then, the gene expression rates of NMDAR1 and HTR1a were measured by the Real-Time PCR. 

Ghrelin and citicoline had some similar and significant effects on passive avoidance memory, and both increased NMDAR1 and decreased HTR1a expression. 

Ghrelin, like citicoline, improves passive avoidance learning by altering the NMDAR1 and HTR1a expression in the hippocampus.

Polycystic ovary syndrome (PCOS) is a complex heterogeneous disease with various symptoms, which can affect females of reproductive age. Endocrine and metabolic abnormalities such as infertility, being over-weight or obese, type 2 diabetes, hyperandrogenism and increased luteinizing hormone (LH) are common in women with PCOS.

This review aimed to assess the efficacy of non-chemical and herbal substances for PCOS recovery. 

The keywords “non-chemical treatment”, “herbal treatment”, “polycystic ovary syndrome” and “PCOS” were used to search for articles in the electronic databases PubMed/MEDLINE, Web of Science, Scopus, and Reaxys, published from January 2009 to December 2019.

34 relevant studies were found and were briefly described in this review. The most effective herbal treatments in animal models of PCOS were to restore abnormality in serum sex steroid profile, LH: follicle stimulating hormone ratio, steroidogenic enzymes, cardiovascular parameters, lipid profile, and glucose and estrous cycles. In PCOS patients, positive effects on PCOS due to reductions in testosterone, estrogen, LH, LH: follicle stimulating hormone ratio, and insulin levels were observed.

The results of this review revealed the variability and efficacy of phytotherapy and non-chemical treatments associated with PCOS disease. These findings may help future studies on the etiology and treatment of this syndrome.

More than 186 million people suffer to infertility worldwide. Polycystic ovary syndrome (PCOS) is the most common cause of chronic anovulation and infertility. PCOS is known as an endocrine disorder in women of marriageable age and is associated with metabolic disorders and dysfunction of the reproductive system. There is also a clear link between fertility and hypothyroidism, which is often associated with ovulation disorders. In recent years, an increasing zest has been witnessed in conducting more research into PCOS and hypothyroidism. So, recognizing the relationship between these two diseases can help for a better understanding of infertility.

In line with such calls for more research, the present study is aimed at investigating the levels of oxidants and antioxidants in the blood of rats with PCOS induced by estradiol valerate (2 mg/kg of body weight) for 60 days and then received oral propylthiouracil in different doses (1,2 and 4 mg/kg of body weight) to induce hypothyroidism.

Results showed an increase in catalase (CAT), superoxide dismutase (SOD) and nitric oxide (NO) in PCOS rats. The results also indicated a significant increase in NO (P<0.05) and a significant decrease in SOD and CAT (P<0.05) after hypothyroidism in rats with PCOS. That is, as the severity of the disease increased, these indicators also showed significant alterations.

Hence, hypothyroidism following PCOS exacerbates oxidant and antioxidant imbalances in the body, which can eventually result in tissue damage.

Coronavirus disease in 2019 (COVID - 19) is a pandemic declared by the World Health Organization after its appearance in the Chinese city of Wuhan in late 2019 . It has infected more than 30 million people worldwide and led to the death of nearly one million of them. Orexin - A (OXA), a neuropeptide produced by the lateral hypothalamic area and several peripheral tissues, regulates appetite, reproduction, and other physiological functions. There are many symptoms associated with infection with the coronavirus, such as a cytokine storm, narcolepsy, impaired senses of smell and taste, and loss of appetite , usually are associated with high or low levels of OXA in the infected people. Moreover, some chronic diseases such as cancer, diabetes, and obesity, generally r eferred to as risk factors for the disease, increase the severity of infection or even lead to death and they are associated with either an increase or a decrease in OXA levels. Moreover, some factors, such as a high testosterone level, facilitate the entr y of a virus into the cells, which OXA controls . In this review, we described for the first time the potential impact of high or low levels of OXA on the severity of the symptoms of COVID - 19 or the death due to this disease

Monosodium glutamate (MSG) is a flavour enhancer that is used as a food additive (E621) in many parts of the world, especially in East Asian countries. However, in recent studies, it has been used as a neurotoxin because MSG is reported to cause neural degeneration in the hypothalamic arcuate of neonatal animals. The results of several studies show the negative effects of MSG injections on different parts of the hypothalamic-pituitary-gonadal (HPG) axis, in addition to its ability to inhibit secretion many reproductive neuropeptides, neurotrophic factors, and hormones, all of which play vital roles in the regulation of reproductive function. Oral administration or injection of large quantities of MSG into newborn animals results in a decrease in or overabundance of the production of many regulatory peptides of the male and female reproductive systems. In this review, we summarize the results of the most important studies that have examined the effect of oral consumption or injection of MSG on regulatory peptides of the HPG axis.

Kisspeptin stimulates gonadotropin releasing hormone (GnRH). The GnRH neurons receive inhibitory inputs from ghrelin, RFamide related peptide-3 (RFRP-3), and gamma-aminobutyric acid (GABA) neurons. Polycystic ovary syndrome (PCOS) is associated with increased levels of GnRH/LH and kisspeptin, and decreased release of GABA, ghrelin, and RFRP-3. In the present study, the effects of GABAB receptor agonist, baclofen, were investigated on GnRH, KiSS1, RFRP-3, and ghrelin gene expression in the hypothalamus of PCOS model rats. For induction of PCOS, female Wistar rats weighing 180-200g received intra-muscular injection of estradiol valerate. Fifteen PCOS rats in three groups received intraperitoneal injections of saline, 5, or 10 mg/kg baclofen for two weeks. The hypothalamic samples were dissected. Gene expression levels of GnRH, KiSS1, RFRP-3, and ghrelin were determined by real time qPCR method. Results revealed that baclofen significantly decreased the mean relative KiSS1 gene expression compared to PCOS group. Also, the mean relative RFRP-3 gene expression significantly increased in the baclofen-receiving rats in comparison to PCOS group. Furthermore, baclofen did not change GnRH or ghrelin mRNA levels in comparison to PCOS group. According to these results it can be concluded that in PCOS condition the GABAergic signaling pathway may suppress GnRH neural activity via down or up regulation of the intra-hypothalamic neuropeptides upstream of GnRH neurons.

In the arcuate nucleus, kisspeptin, neurokinin-B and pro-dynorphin (KNDy) neurons control the function of gonadotropin-releasing hormone (GnRH) neurons. Early investigations indicated that exercise with various intensities affects luteinizing hormone (LH) and testosterone (T) in different ways. Meanwhile the molecular mechanisms underlying its function not yet been fully understood. Accordingly, the present study evaluated the role of alterations in the levels of KNDy mRNA upstream of GnRH neurons in conveying the effects of various short-term exercise intensities on the male hypothermic-pituitary-gonadal (HPG) axis.

Twenty-one adult Wistar rats were randomly divided into 3 groups: control, one-month regular moderate exercise (ME) and one-month regular intensive exercise (IE). In ME (22m/min) and IE (35m/min) groups, the rats were treated 5 days a week for 60min each day. Finally, we assessed serum levels of LH and T using the ELIZA technique and KNDy and Gnrh mRNA expression by the real-time PCR method.

The results revealed that in ME group the expression of Nkb was reduced and the expression of Gnrh mRNA and the LH and T serum levels were increased. However, intensive exercise did not change the serum levels of LH and T or the relative expression of kiss1, Nkb, Pdyn and Gnrh genes.

The results suggested that monthly moderate exercise improved male reproductive axis function, while intensive exercise did not have an adverse effect on the reproductive axis. These various effects on the male HPG axis may be propagated by the change in hypothalamic Nkb gene expression.

Motor learning consolidates in adulthood, and its defects begin to appear with aging. Ghrelin, an endogenous peptide, improves memory and learning, targeting dopaminergic circuits. While cytidine diphosphate choline (citicoline) is known as a common drug for enhancing memory and learning in aging, it is not recommended for adults due to its side effects. The current study aimed at investigating if ghrelin treatment would improve motor learning via the expression of a relevant gene.

For this experimental study, adult male Wistar rats were randomly divided into five groups: control group, three groups of ghrelin treatment (0.3, 1.5, and 3 nmol/μL), and one group with citicoline treatment. The injections were done intra-hippocampally. The motor learning rate was determined using the rotarod performance test by measuring the resistance to falling. Then the expression of dopamine receptor type D1 (Drd1) gene in the hippocampus was measured by a real-time polymerase chain reaction (PCR).

Ghrelin (3 nmol/μL) and citicoline had similar and significant effects on motor learning improvement (P<0.01). Both drugs significantly increased Drd1 gene expression (P <0.001).

Ghrelin, like citicoline, improves motor learning by altering the expression of Drd1 gene in the hippocampus.

This study was investigated the interaction effects of the intra-hippocampal injection of citalopram with estrogen and progesterone on passive avoidance memory and motor balance in male Wistar rats.

This experimental study was conducted on the 25 male Wistar rats. Passive avoidance memory measured by shuttle box device and movement balance examined by the rotarod device. Animal randomly assigned into 5 groups, group 1: saline, group 2: citalopram (2 nmol), group 3: citalopram (2 nmol) + estrogen (1 nmol), group 4: citalopram (2 nmol) + progesterone (1 nmol), and group 5 citalopram (2 nmol) + estrogen (1 nmol) + progesterone (1 nmol). In all groups, the final injection volume was 1.5 μl in left or right hippocampi.

Citalopram received group increased the latency for entering the dark areas and the total time the animals have spent in the light compartment. It shows that citalopram has increased passive avoidance memory (p < 0.001). When the citalopram was injected with steroid hormones into the hippocampus, there was a significant increase in learning and memory activity in rats (p < 0.01). In the motor balance test initially, there was no significant difference observed between the control groups. After receiving the injections at 1,3 and 24-h intervals, a significant decrease in motor balance was observed compared to the other control groups (p < 0.01).

Intra-hippocampal injection of citalopram increased the passive avoidance learning process in rats receiving the drug. On the other hand, citalopram reduces motor balance when combined with estrogen and progesterone.