Exploration of the white matter bundles connected to the pineal gland: A DTI study.

PURPOSE: Pineal gland (PG) is a structure located in the midline of the brain, and is considered as a main part of the epithalamus. There are reports on the role of this area for brain function by hormone secretion, as well as few reports on its role in brain cognition. However, little knowledge is available on the PG, and in particular on the structural connectivity of this region with the other brain structures. METHODS: Using diffusion-weighted images collected by a 3T MRI scanner, and using a sample of 61 (29 F) mentally and physically healthy young individuals in the age range of 20-30 years old, we tried to extract the white matter bundles connected to the PG. Based on prior knowledge, seven target bundles were suggested to be between the PG body and the PG roots, Pons, Periventricular region, thalamus, caudate, lentiform, suprachiasmatic nuclei, and the supercervical ganglia. RESULTS: Nearly all the target bundles were successfully extracted, with the exception of the lentiform. Rate of identification of the tracts was different, with the bundle between the PG body and roots having the highest identification rate (97%); then it was with the Pons (70%), Periventricular region (57%), SCN (55%), left thalamus (52%), right thalamus (47%), left caudate (27%) and right caudate (22%). CONCLUSION: This study is an attempt to expand our knowledge on the neuroanatomy of the PG, which might help for identifying further roles for it in brain functionality, and also be a help for the treatment of some disorders in the future.

Effect of eugenol on lipid profile, oxidative stress, sex hormone, liver injury, ovarian failure, and expression of COX-2 and PPAR-α genes in a rat model of diabetes.

BACKGROUND: Diabetes is among the leading causes of reproductive system failure and infertility in both women and men. Inflammation and oxidative stress have a main role in the development of diabetes. Eugenol or clove oil is a phenolic monoterpenoid with antioxidant and anti-inflammatory properties. Here, the effects of eugenol on diabetes features and ovarian function were investigated. METHODS AND RESULTS: Streptozotocin-induced diabetes rats were treated with 12 and 24 mg/kg of eugenol for 4 weeks. The biochemical and histological assay was done to evaluate the effects of eugenol on ovary and pancreas function, liver injury, oxidative status, sex hormones, lipid profile, and mRNA levels of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor alpha (PPAR-α) genes. Streptozotocin increased levels of serum glucose, total cholesterol, triglyceride, low-density lipoprotein, aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, pancreas necrosis and inflammation, COX-2 expression, ovarian cystic, and anovulation. It decreased the levels of insulin, high-density lipoprotein, Superoxide dismutase, estradiol, progesterone, testosterone, luteinizing hormone, follicle-stimulating hormone, and PPAR-α expression. Eugenol administration ameliorated diabetes features through the improvement of lipid profile, oxidative status, insulin and glucose levels, sex hormone levels, liver markers, COX-2 and PPAR-α expression, and pancreas histology. It had no effect on ovarian cystic and follicular development. CONCLUSIONS: Therefore, eugenol may be useful for ameliorating some adverse features of diabetes and used as an adjunct treatment or protective agent accompany by other chemicals in diabetes patients.

Apelin-13 protects against memory impairment and neuronal loss, Induced by Scopolamine in male rats.

The present study aimed to evaluate the effects of Apelin-13 on scopolamine-induced memory impairment in rats. Forty male rats were divided into five groups of eight. The control group received no intervention; the scopolamine group underwent stereotaxic surgery and received 3 mg/kg intraperitoneal scopolamine. The treatment groups additionally received 1.25, 2.5 and 5 µg apelin-13 in right lateral ventricles for 7 days. All rats (except the control group) were tested for the passive avoidance reaction, 24 h after the last drug injection. For histological analysis, hippocampal sections were stained with cresyl violet; synaptogenesis biochemical markers were determined by immunoblotting. Apelin-13 alleviated scopolamine-induced passive avoidance memory impairment and neuronal loss in the rats' hippocampus (P<0.001). The reduction observed in mean concentrations of hippocampal synaptic proteins (including neurexin1, neuroligin, and postsynaptic density protein 95) in scopolamine-treated animals was attenuated by apelin-13 treatment. The results demonstrated that apelin-13 can protect against passive avoidance memory deficiency, and neuronal loss, induced by scopolamine in male rats. Further experimental and clinical studies are required to confirm its therapeutic potential in neurodegenerative diseases.

Comparing various protocols of human and bovine ovarian tissue decellularization to prepare extracellular matrix-alginate scaffold for better follicle development in vitro.

BACKGROUND: Nowadays, the number of cancer survivors is significantly increasing as a result of efficient chemo/radio therapeutic treatments. Female cancer survivors may suffer from decreased fertility. In this regard, different fertility preservation techniques were developed. Artificial ovary is one of these methods suggested by several scientific groups. Decellularized ovarian cortex has been introduced as a scaffold in the field of human fertility preservation. This study was carried out to compare decellularization of the ovarian scaffold by various protocols and evaluate the follicle survival in extracellular matrix (ECM)-alginate scaffold. RESULTS: The micrographs of H&E and DAPI staining confirmed successful decellularization of the ovarian cortex in all experimental groups, but residual DNA content in SDS-Triton group was significantly higher than other groups (P < 0.05). SEM images demonstrated that complex fiber network and porosity structure were maintained in all groups. Furthermore, elastin and collagen fibers were observed in all groups after decellularization process. MTT test revealed higher cytobiocompatibility of the SDS-Triton-Ammonium and SDS-Triton decellularized scaffolds compared with SDS groups. Compared to the transferred follicles into the sodium alginate (81%), 85.9% of the transferred follicles into the decellularized scaffold were viable after 7 days of cultivation (P = 0.04). CONCLUSION: Although all the decellularization procedures was effective in removal of cells from ovarian cortex, SDS-Triton-Ammonium group showed less residual DNA content with higher cytobiocompatibility for follicles when compared with other groups. In addition, the scaffold made from ovarian tissues decellularized using SDS-Triton-Ammonium and sodium alginate is suggested as a potential 3D substrate for in vitro culture of follicles for fertility preservation.

Combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by chlorpyrifos.

The aim of this study was to investigate the combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by CPF. 64 adult male albino rats were randomly selected and devided into eight groups of eight including: control, exercise (EXE), chlorpyrifos (CPF), Control + Oil (Co + Oil), Control + DMSO (Co + DMSO), chlorpyrifos + eugenol (CPF + Sup), chlorpyrifos + exercise (CPF + Exe) and, chlorpyrifos + exercise + eugenol (CPF + Exe + Eu). Four experimental groups received intraperitoneal injection (5 days a week) of 3.0 mg/kg body weight CPF in DMSO for 6 consecutive weeks. The exercise groups performed aerobic 5 days per week over 4 weeks. Eugenol were administered by gavage. Finally, the animals were sacrificed using CO2 gas (a half of the rats were anesthetized with ketamine and xylazine and then perfused) to evaluate hippocampus histology and parameters. The results of this study showed that CPF injection significantly decreased BDNF, AChE and ATP in CA1 area of the hippocampus (p ˂ 0.05). Also, CA1 apoptosis by tunnel assay, it was found that CPF receiving groups with different dosage, showed a significant increase compared to other groups, which was confirmed by increasing cytochrome C and procaspase-3 in CPF groups (p ˂ 0.05). The result of this study show that 4 weeks of exercise training and eugenol supplementation does not improve the destructive effects of CPF in CA1 area of the hippocampus. As a result, it is recommended that future studies longer periods for treatment with exercise and eugenol supplementation.

Simultaneous use of sensory stimulation and motor exercise improves the manual skills of educable children with mental retardation at preprimary and primary school levels.

Background: Children with mental retardation have various clinical problems. They mostly have motor delay and sensory deficit. Neurorehabilitation focuses on restoring remaining abilities. Thus, the present study was designed to study the effects of simultaneous use of sensory-motor therapy on manual skills of children with mental retardation. Methods: In this study, 120 educable boys and girls with mental retardation (9-12 years) were selected from 2 preprimary and primary exceptional centers in Tehran using stratified sampling method considering the geographical dispersion. The participants were divided into 2 equal trial and control groups using simple random sampling. Lincoln-Oseretsky Motor Development Scale, Purdue Pegboard test, and Handwriting Legibility Checklist of Persian Language were used. Simultaneous sensory stimulations and motor exercises were used for 3 one-hour weekly sessions for 12 consecutive weeks. Pre and posttests were done for evaluation. Using parametric paired and independent samples t tests, the findings were analyzed in SPSS 23. Results: The manual skills significantly improved following therapeutic use of simultaneous sensory stimulation and motor exercise (p=0.001). In the control group, the pre and post evaluation difference was not significant (p=0.813) Conclusion: Based on the findings of this study, simultaneous use of sensory-motor techniques can have better clinical results in the trial group compared to the control group. Thus, these types of techniques should be used more in clinics. However, further studies are needed for more comparison between separate applications of these techniques.

Swimming Training Attenuates Allodynia and Hyperalgesia Induced by Peripheral Nerve Injury in an Adult Male Rat Neuropathic Model: Effects on Irisin and GAD65.

Objective: The analgesic mechanism of long-lasting exercise on neuropathic pain is not well understood. This study explored the effects of swimming training on neuropathic pain and the expression of irisin, GAD65, and P2X3 after chronic constriction injury (CCI) of the sciatic nerve. Methods: Thirty-five male rats were randomly assigned to one of the following five groups: 1) no CCI or swimming (control); 2) swimming without CCI (SW); 3) swimming with CCI (CCISW); 4) CCI without swimming (CCI); and 5) sham CCI surgery (sham CCI). Behavioral responses to mechanical, cold, and heat stimuli were tested before and after CCI surgery, as well as each week throughout the four weeks of swimming training. The expression of irisin, GAD65, and P2X3 proteins in L4-L6 spinal cord segment, ipsilateral to the nerve injury, were evaluated by western blotting. Results: Mechanical hyperalgesia was alleviated between the second and fourth weeks of training in the CCISW group. In the tactile allodynia and heat hyperalgesia tests, withdrawal thresholds of the CCISW group were significantly higher than the CCI group at the third and fourth week of training (P < 0.05), while cold allodynia showed delayed improvement occurring by the fourth week of training. The expression of irisin was lower in the CCISW and SW groups compared with the CCI group at day 33 post-CCI surgery. Moreover, CCI surgery significantly decreased the protein expression of GAD65 in L4-L6 spinal cord segments (P = 0.018), whereas swimming training prevented the decline of GAD65 in the CCISW group. Conclusions: Our findings showed that four weeks of swimming training produce beneficial rehabilitative effects on neuropathic pain symptoms. The analgesic effect of swimming training is partially related to the increase of GAD65. The beneficial role of irisin in neuropathic pain will require further investigation.

Combined therapeutic effects of low power laser (980nm) and CoQ10 on Neuropathic Pain in adult male rat.

BACKGROUND: Neuropathic pain (NP) is one of the most suffering medical conditions that often fail to respond to certain pain therapy. Although its exact etiology is still unknown the role of reactive oxygen species (ROS) and oxidative stress were explored by many researchers. Neuropathies either central or peripheral lead to painful condition as well as social and economic isolation, thus various therapies were used to treat or reduce the pain. Laser therapy and antioxidant drugs have separately considered as treatment for NP, but the combination of them have not been used yet. In order to study the combination effects of Low Level Laser Therapy (LLLT) and Coenzyme Q10 (CoQ10) the present study was designed. METHODS: Sixty adult male rats (230-320g) were used in this experimental study that divided into six groups (n=10). Chronic constriction injury (CCI) was used to induce neuropathic pain. The CoQ10 or vehicle, a low level laser of 980nm was used for two consecutive weeks. Thermal and mechanical paw withdrawal thresholds were assessed before and after surgery on 7(th) and 14(th) days. RESULTS: As we expected CCI decreased the pain threshold, whereas CoQ10 administration for two weeks increased mechanical and thermal threshold. The same results obtained for laser therapy using the CCI animals. Combination of laser 980nm with CoQ10 also showed significant differences in CCI animals. CONCLUSION: Based on our findings the combination of CoQ10 with LLLT showed better effects than each one alone. In this regard we believe that there might be cellular and molecular synergism in simultaneous use of CoQ10 and LLLT on pain relief.

Therapeutic Effects of Low-Level Laser Therapy on Pain and Disability of Patients with Failed Back Surgery Syndrome.

Purpose: This study intended to evaluate the effects of Low-Level Laser Therapy (LLLT) on Failed Back Surgery Syndrome (FBSS). FBSS refers to symptoms and disabilities which remain or occur after lumbar spinal surgery. Prevalent treatments for FBSS are based mostly on conservative management while LLLT has gained significant interest in the treatment of a wide variety of musculoskeletal disorders. Methods: In the present study, the authors included 50 individuals with FBSS. Target points were determined by an ultrasonic study including bilateral L2-L3 through L5-S1 facet joints, sacroiliac joints, and the region immediately above bilateral supra crestal iliac bones representing cluneal nerves. LLLT was performed three times a week for 3 weeks. A near-infrared laser (wavelength 808 nm, power 500 mw) was used in continuous mode for laser therapy sessions. The Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI) were registered before treatment and after last treatment session, 1 month and 6 months later, respectively. Results: NRS and ODI were significantly improved after treatment, as well as therapeutic effects, after 1 month and 6 months were also evident and comparison of the NRS and ODI showed significant difference. Conclusion: LLLT has a positive impact on pain and disability in patients with FBSS.

Effect of sex differences and time of oxytocin administration on treatment of rat model of autism spectrum disorder: Focused on necroptosis markers.

Autism is a neurodevelopmental disorder. A variety of molecular and cellular abnormalities leads to behavioral deficits in autism. Nevertheless, its etiology and treatment strategy are not completely understood. Oxytocin has recently shown improvements in social functioning. This study aimed to evaluate the necroptosis pathway for the neuroprotective effects of oxytocin in the valproic acid-induced autism spectrum disorder model. The autism spectrum disorder was induced by valproic acid on gestational day 12.5 (600 mg/kg, intraperitoneally). Offspring received intranasal oxytocin (1 µg/µL) on the 21st and 40th days after birth. The offspring behaviors were scrutinized by self-grooming, marble-burying, three-chamber, and Morris water maze tests. Western blot was performed on the hippocampus and amygdala tissues to investigate the expression of RIP3 and MLKL markers. The valproic acid group demonstrated more anxiety, repetitive behaviors, and expression of RIP3 and MLKL markers, and less social interaction and spatial memory compared with the control group. Oxytocin considerably improved social interactions, preference for social novelty, and memory. The elevated expression of RIP3 and MLKL markers in valproic acid-induced autistic rats were alleviated after treatment with oxytocin. We also highlighted the importance of age and gender in autism spectrum disorder interventions. Our findings suggested that oxytocin administration was as an effective treatment in two areas of repetitive/stereotyped behaviors, social interactions/cognitive function. Notably, early administration of oxytocin resulted in better therapeutic responses in autism-like behaviors. The molecular tests introduce oxytocin as a potential candidate for reducing the expression of necroptosis mediators in the brain. This reinforced our hypothesis that the necroptosis pathway takes part in autism spectrum disorder.

Health related quality of life and pain characteristics among Iranian patients suffering non-malignant chronic pain.

BACKGROUND: Chronic pain is a frequent disability that negatively affects patient's quality of life. Understanding of the possible relation between sociodemographic and medical variables with Health Related Quality of Life (HRQL) may help identifying the multidimensionality of pain and risk factors that limit physical and psychological adjustment of the patients. The present study was done to find these possible relationships, based on using Medical Outcomes Survey-Short Form (SF-36). METHODS: Among the patients who were referred to pain clinic of Iranian Pain Society, 101 consecutive outpatients were select based on the defined inclusion and exclusion criteria. All the participants in this study orally satisfied and were fully informed by a check list and SF-36 questionnaire. The possible impact of demographic variables, characteristics, diagnosis, analgesic use, smoking and opium addiction were collected as the first part of a routine pretreatment evaluation. RESULTS: Our findings showed significant relation between HRQL and gender (P < 0.05), the rate of chronic pain in female was higher than male, and same results found for elderly patients compared to younger ones. Our findings also showed significant relation between employment and intensity of pain (p = 0.001) as, employed patients showed less physical and psychotic problems than unemployed ones. The mean average of intensity of pain in these patients was 7.5±2.2; few patients used alcohol (4%), opium (1%) and cigarette (10%). Large number of participants used analgesic (%78.2). No significant difference between sociodemographic features with pain duration and quality of life was found. In contrast our data showed significant difference between pain intensity and quality of life (p < 0.001). CONCLUSION: Based on our findings it could be concluded that chronic pain in Iranian patients certainly leads to poor HRQL, the state is more serious in the elderly and female patients. Thus, in order to re-socialize the patients suffering chronic pain and decrease the impact of their pain on their life, these findings should be considered in any kind of pain relief therapy.

Therapeutic Effects of Eugenol in Polycystic Ovarian Rats Induced by Estradiol Valerate: A Histopathological and A Biochemical Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common type of endocrinopathy in women which is accompanied by androgens elevation, insulin resistance, and metabolic dysfunction. Eugenol is a phenolic component of clove oil that has an antioxidant, anti-inflammatory, and anti-diabetic activity. The present study aimed to evaluate the therapeutic effects of eugenol on the PCOS models of rats. MATERIALS AND METHODS: In this experimental study, thirty adults female Wistar rats weighing between 180 and 200 g were used. Estradiol valerate-induced PCOS rats (4 mg/rat) were treated with eugenol (12 and 24 mg/kg) for 28 days. The effects of eugenol were studied on levels of glucose, lipid profile, liver enzymes, reproductive hormones, oxidative stress, and the expression of cyclooxygenase-2 (Cox-2) and peroxisome proliferator-activated receptor alpha (Ppar-α) genes, using biochemical analysis of blood and histopathological evaluation of ovaries.
Results: Estradiol valerate-induced PCOS resulted in the formation of cystic follicles in the ovaries, hyperinsulinemia, hyperglycemia, hyperlipidemia, hyperandrogenism, and anovulation. It altered the Cox-2 and Ppar-α gene expression and increased oxidative stress and activities of liver enzymes. Eugenol treatment improved the PCOS-associated endocrine and metabolic disorder and histopathological alterations, mostly through antioxidant, anti-diabetic, anti hyperlipidemic, and anti-androgenic properties. It showed beneficial effects on serum glucose, serum insulin, fat profile, reproductive hormones, liver activity, oxidative stress, expression of Cox-2 and Ppar-α genes, as well as restoration of normal ovulation in the PCOS animals.
Conclusion: Eugenol could represent a promising natural product to prevent PCOS or reduce its symptoms.

All-Trans Retinoic Acid-Preconditioned Mesenchymal Stem Cells Improve Motor Function and Alleviate Tissue Damage After Spinal Cord Injury by Inhibition of HMGB1/NF-κB/NLRP3 Pathway Through Autophagy Activation.

Spinal cord injury (SCI) is a significant public health issue that imposes numerous burdens on patients and society. Uncontrolled excessive inflammation in the second pathological phase of SCI can aggravate the injury. In this paper, we hypothesized that suppressing inflammatory pathways via autophagy could aid functional recovery, and prevent spinal cord tissue degeneration following SCI. To this end, we examined the effects of intrathecal injection of all-trans retinoic acid (ATRA)-preconditioned bone marrow mesenchymal stem cells (BM-MSCs) (ATRA-MSCs) on autophagy activity and the HMGB1/NF-κB/NLRP3 inflammatory pathway in an SCI rat model. This study demonstrated that SCI increased the expression of Beclin-1 (an autophagy-related gene) and NLRP3 inflammasome components such as NLRP3, ASC, Caspase-1, and pro-inflammatory cytokines IL-1ß, IL-18, IL-6, and TNF-α. Additionally, following SCI, the protein levels of key autophagy factors (Beclin-1 and LC3-II) and HMGB1/NF-κB/NLRP3 pathway factors (HMGB1, p-NF-κB, NLRP3, IL-1ß, and TNF-α) increased. Our findings indicated that ATRA-MSCs enhanced Beclin-1 and LC3-II levels, regulated the HMGB1/NF-κB/NLRP3 pathway, and inhibited pro-inflammatory cytokines. These factors improved hind limb motor activity and aided in the survival of neurons. Furthermore, ATRA-MSCs demonstrated greater beneficial effects than MSCs in treating spinal cord injury. Overall, ATRA-MSC treatment revealed beneficial effects on the damaged spinal cord by suppressing excessive inflammation and activating autophagy. Further research and investigation of the pathways involved in SCI and the use of amplified stem cells may be beneficial for future clinical use.

Dopamine D1 Receptor-Mediated Regulation of Per1, Per2, CLOCK, and BMAL1 Expression in the Suprachiasmatic Nucleus in Adult Male Rats.

Photic and non-photic inputs are reported to affect clock gene expressions and behavioral activities in the SCN. However, it is not known whether dopaminergic input mediates these regulatory effects on clock genes. The present study examined the molecular effects of dopamine D1 agonist on Per1, Per2, CLOCK, and Bmal1 expressions in the SCN and its effect on behavioral activities to determine the role of dopamine D1 receptor in regulation of these gene expressions and behavioral activities in adult male Wistar rats. To examine the molecular effects of dopamine D1 agonist day and night, we injected 20 mg/kg SKF38393 to the first group of rats at 6 a.m. and the second group at 6 p.m. We also injected saline to the third and fourth groups of rats at 6 a.m. and 6 p.m. as control groups. All rats were sacrificed 2 h following the injections. The real-time PCR technique was used to evaluate the clock gene expression. In addition, to examine the effects of dopamine D1 agonists on behavioral activities, we injected 20 mg/kg SKF38393 to SKF receiving group and saline to control group. The behavioral activities of the rats were monitored on the running wheel for 21 days, 1 week following the injections. SKF injections increased the Per2 and CLOCK expressions in the daytime and significantly decreased the Per1 and Bmal1 expressions. However, at night, SKF injections increased only Per2 expressions significantly and decreased the Per1, CLOCK, and Bmal1 genes expressions. Both saline receiving groups showed that all gene expressions were significantly higher except Per2 during nighttime. SKF injection increased the running wheel activity during nighttime significantly. Based on the obtained result, clock gene expression and behavioral activities in adult male Wistar rats may be altered or monitored by administration of exogenous dopamine.

The Effect of Resistance Training and Berberine Chloride on the Apoptosis-related Unfolded Protein Response Signaling Pathway in the Hippocampus of Diazinon-poisoned Rats.

INTRODUCTION: Diazinon is one of the most widely-used organophosphate pesticides in the world. This toxin enters the body in various ways and induces oxidative stress in various tissues. It has been proved that activation of Unfolded Protein Response (UPR) under oxidative stress is a steady mechanism for maintaining cell function and survival. Therefore, the present study aimed to review the effect of Resistance Training (RT) and Berberine Chloride (BC) on the apoptosis-related UPR signaling pathway in the hippocampus of diazinon-poisoned rats. METHODS: In this experimental study, 40 male Wistar rats weighing 250 ±50 g were randomly divided into eight groups of five rats of 1) diazinon + 2 mg/kg BC + RT, 2) diazinon + 15 mg/kg BC + RT, 3) diazinon, 4) diazinon + RT, 5) diazinon + 2 mg/kg BC, 6) diazinon + 15 mg/kg BC, 7) healthy control, and 8) sham. The groups were treated for 5 weeks. At the end of the fifth week, ATF-4, ATF-6, and CHOP gene expression in hippocampus tissue were measured by quantitative real-time RT-PCR. RESULTS: Diazinon significantly increased the expression of ATF-4, ATF-6, and CHOP in the hippocampus tissue of rats. Administrating 15 mg/kg BC with RT significantly decreased these genes, indicating a decrease in the rate of apoptosis in the hippocampus. CONCLUSION: This study showed that RT and BC have a protective effect against diazinon-induced toxicity in the hippocampus.

Neurogenesis in the rat neonate's hippocampus with maternal short-term REM sleep deprivation restores by royal jelly treatment.

BACKGROUND: Numerous studies have shown the effects of rapid eye movement sleep deprivation (REM-SD) on behavior and brain structures. The impact of REM-SD on learning and memory, thus neurogenesis, has been reported in previous studies. Royal jelly (RJ) is known as the wealthiest biological nutrient with various physiological properties. This study aimed to study the possible effect of RJ on neurogenesis of the rat hippocampus neonates following exposure of mother to REM-SD during pregnancy. METHODS: Thirty neonate rats from 15 pregnant Wistar rats were used. To induce REM-SD, the flowerpot method was used. The pregnant rats were divided into five groups (n = 3): group 1, no treatment; group 2, REM-SD; groups 3, 4, and 5, REM-SD +RJ. The former group received 72 h REM-SD during pregnancy (days 7, 14, 21), and the latter group received REM-SD + RJ (three trial groups). At week 4, the rat neonates of all groups were sacrificed (n = 6 each group). Their brains were fixed, removed, and prepared for Nissl and Hoechst 33342 staining. By using real time polymerase chain reaction methode the brain-derived neurotrophic factor BDNF gene expression was studied (RT-PCR), brain-derived neurotrophic factor (BDNF) gene expression was studied. The results were analyzed statistically, and the Pv  < .05 was considered significant. RESULTS: The results showed a significant decrease in the number of neurons in the hippocampus of neonatal rats of REM-SD mothers compared to the neonates of the mother with REM-SD + RJ. REM-SD also led to an increase in apoptosis reaching the neonates from the REM-SD + RJ animals. High expression of BDNF was observed in the hippocampus of the neonates from REM-SD + RJ treated mothers. CONCLUSION: RJ acts as a neuroprotective agent that could compensate for the effects of REM-SD on learning and memory via restoring neurogenesis.

The effectiveness of continuous and interval exercise preconditioning against chronic unpredictable stress: Involvement of hippocampal PGC-1α/FNDC5/BDNF pathway.

Various exercise-training types are known to prevent depression, but mechanisms underlying their beneficial effects remain unknown. In the present study, the preconditioning effect of continuous and interval exercise on stress-induced depression was evaluated. Adult male Wistar rats in the exercise groups were made to run on a motorized treadmill, five sessions per week for six weeks. After that, to induce the depression model, the rats were exposed to chronic unpredictable stress for three weeks. Behavioral tests were assessed by open field, elevated plus maze, and forced swim tests. Hippocampal PGC-1α, FNDC5, and BDNF protein expression by Western blot and serum corticosterone by ELISA were detected. In the present results, after continuous and interval exercise periods, locomotor activity, the number of entries and time spent in the open arms were increased, and immobility time was significantly reduced. PGC-1α, FNDC5, and BDNF protein levels had a significant increase, and serum corticosterone did not change. Also, interval exercise training increased PGC-1α and FNDC5 more than continuous. Chronic unpredictable stress reduced the positive changes caused by exercise training, although, except FNDC5, exercise preconditioned groups experienced less significant adverse changes in most variables. These findings showed that both continuous and interval exercise preconditioning with increasing hippocampal PGC-1α, FNDC5, and BDNF proteins and improve the anxiety- and depression-like behaviors have a protective effect against chronic unpredictable stress.

ß-Amyloid Formation, Memory, and Learning Decline Following Long-term Ovariectomy and Its Inhibition by Systemic Administration of Apigenin and ß-Estradiol.

INTRODUCTION: The increasing cases of Alzheimer Disease (AD) has caused numerous problems. The risk of developing AD increases in menopausal women, too. Apigenin and ß-estradiol are effective antioxidant and neuroprotective agents. We conducted the present study to explore their combined effects on ß-amyloid plaque formation, memory, and learning in ovariectomized rats. METHODS: Forty-two Wistar rats were randomly assigned into 6 groups: 1) ovariectomized (OVX), 2) OVX + apigenin, 3) OVX + ß-estradiol, 4) OVX + apigenin + ß-estradiol, 5 &6) vehicle shams for E2 and API, and 7) surgical sham. Treatment was done with apigenin and ß-estradiol. Then, we studied the formation of ß-amyloid plaques, neuronal density in the hippocampus area, apoptosis, memory, and learning. RESULTS: Findings showed the significant formation of ß-amyloid plaques in the hippocampus of OVX animals and their memory impairment. Apigenin and ß-estradiol significantly reduced the number of ß-amyloid plaques, as well as the symptoms of memory impairment and learning, and decreased the expression of caspase-3 in treated animals. CONCLUSION: Accordingly, ß-estradiol and apigenin could have more potent therapeutic effects on AD.

Related Fluoxetine and Methylprednisolone Changes of TNF-α and IL-6 Expression in The Hypothyroidism Rat Model of Spinal Cord Injury.

OBJECTIVE: Spinal cord injury (SCI) is a serious clinical condition that leads to disability. Following primary injury, proinflammatory cytokines play an important role in the subsequent secondary events. The thyroid hormone (TH) is known as the modulator of inflammatory cytokines and acts as a neuroprotective agent. Methylprednisolone (MP) is used for the early treatment of SCI. Fluoxetine (FLX), also is known as a selective serotonin reuptake inhibitor (SSRI), has therapeutic potential in neurological disorders. The aim of the present study was to investigate the combined effects of MP and FLX on SCI in the rat hypothyroidism (hypo) model. MATERIALS AND METHODS: In this experimental study, 48 male Wistar rats with hypothyroidism were randomly divided into 6 groups (n=8/group): control (Hypo), Hypo+Surgical sham, Hypo+SCI, Hypo+SCI+MP, Hypo+SCI+FLX, and Hypo+SCI+MP+FLX. SCI was created using an aneurysm clip and Hypothyroidism was induced by 6-Propyl-2-thiouracil (PTU) at a dose of 10 mg/kg/day administered intraperitoneally. Following SCI induction, rats received MP and FLX treatments via separate intraperitoneal injections at a dose of 30 and 10 mg/kg/day respectively on the surgery day and FLX continued daily for 3 weeks. The expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were quantified by Real-time polymerase chain reaction (PCR) and Western blotting. Myelination and glutathione (GSH) levels were analyzed by Luxol Fast Blue (LFB) staining and ELISA respectively. RESULTS: Following combined MP and FLX treatments, the expression levels of TNF-α and IL-6 significantly decreased and GSH level considerably increased in the trial animals. CONCLUSION: Our results show the neuroprotective effects of MP and FLX with better results in Hypo+SCI+MP+FLX group. Further study is required to identify the mechanisms involved.

More attention on glial cells to have better recovery after spinal cord injury.

Functional improvement after spinal cord injury remains an unsolved difficulty. Glial scars, a major component of SCI lesions, are very effective in improving the rate of this recovery. Such scars are a result of complex interaction mechanisms involving three major cells, namely, astrocytes, oligodendrocytes, and microglia. In recent years, scientists have identified two subtypes of reactive astrocytes, namely, A1 astrocytes that induce the rapid death of neurons and oligodendrocytes, and A2 astrocytes that promote neuronal survival. Moreover, recent studies have suggested that the macrophage polarization state is more of a continuum between M1 and M2 macrophages. M1 macrophages that encourage the inflammation process kill their surrounding cells and inhibit cellular proliferation. In contrast, M2 macrophages promote cell proliferation, tissue growth, and regeneration. Furthermore, the ability of oligodendrocyte precursor cells to differentiate into adult oligodendrocytes or even neurons has been reviewed. Here, we first scrutinize recent findings on glial cell subtypes and their beneficial or detrimental effects after spinal cord injury. Second, we discuss how we may be able to help the functional recovery process after injury.