The role of glutamate NMDA receptors of the mediodorsal thalamus in scopolamine-induced amnesia in rats.

The current study was designed to examine the role of glutamate NMDA receptors of the mediodorsal thalamus (MD) in scopolamine-induced memory impairment. Adult male rats were bilaterally cannulated into the MD. According to the results, intraperitoneal (i.p.) administration of scopolamine (1.5 mg/kg) immediately after the training phase (post-training) impaired memory consolidation. Bilateral microinjection of the glutamate NMDA receptors agonist, N-Methyl-D-aspartic acid (NMDA; 0.05 µg/rat), into the MD significantly improved scopolamine-induced memory consolidation impairment. Co-administration of D-AP5, a glutamate NMDA receptor antagonist (0.001-0.005 µg/rat, intra-MD) potentiated the response of an ineffective dose of scopolamine (0.5 mg/kg, i.p.) to impair memory consolidation, mimicking the response of a higher dose of scopolamine. Noteworthy, post-training intra-MD microinjections of the same doses of NMDA or D-AP5 alone had no effect on memory consolidation. Moreover, the blockade of the glutamate NMDA receptors by 0.003 ng/rat of D-AP5 prevented the improving effect of NMDA on scopolamine-induced amnesia. Thus, it can be concluded that the MD glutamatergic system may be involved in scopolamine-induced memory impairment via the NMDA receptor signaling pathway.

Impacts of an 8-week regimen of aged garlic extract and aerobic exercise on the levels of Fetuin-A and inflammatory markers in the liver and visceral fat tissue of obese male rats.

BACKGROUND & AIMS: Obesity-induced chronic low-grade systemic inflammation is linked to the development of numerous diseases. Fetuin-A is known to affect inflammation and insulin resistance in obesity conditions. Free fatty acid (FFA)-induced proinflammatory cytokine expression in adipocytes occurs only in the presence of both Fetuin-A and toll-like receptor 4 (TLR4) and removing either of them prevented FFA-induced insulin resistance. Aged garlic extract (AGE) and exercise training have anti-inflammatory effects; however, the impact of AGE on Fetuin-A is unknown. We examined the effects of AGE with or without aerobic training (AT) on Fetuin-A and inflammatory markers. METHODS: Forty healthy male Sprague Dawley rats were randomly assigned to normal diet (ND) (n = 8) or high-fat diet (HFD) groups (n = 32) and fed for 9 weeks. After 9 weeks ND group continued normal diet, and the HFD group was randomly assigned to the HFD, HFD + AGE (600 mg/kg, once daily), HFD + AT (5 days/week), and HFD + AGE + AT groups that were continued for 8 weeks (n = 8). The significance of differences among groups was assessed using one-way analysis of variance followed by the post-hoc Tukey test. Statistically significant differences were considered for p < 0.05. RESULTS: AGE, AT, and AGE + AT significantly decreased body weight, plasma Fetuin-A, HOMA-IR, mRNA and protein levels of Fetuin-A and NFƙB in the liver and mRNA and Protein levels of Fetuin-A, TLR4 and NFƙB in visceral adipose tissue (VAT) compared to HFD. However, only AGE + AT significantly decreased TLR4 protein levels in the liver. CONCLUSION: Although AT and AGE reduce Fetuin-A and inflammatory markers, a combination of the two may be more effective at lowering inflammation.

The effects of kindling during pregnancy on long-term potentiation (LTP) induction and M1 muscarinic acetylcholine receptors in male rat offspring.

Background and purpose: Neonates of pregnant women with epilepsy may compromise normal neurodevelopment and hippocampal morphology. Memory and learning disorders and a decrease in verbal IQ scores are seen in these children later in life. In the previous study, we suggested that the central muscarinic cholinergic receptors had an important role in learning and memory deficits induced by prenatal pentylenetetrazol-kindling in pups born to kindled mothers. This study aimed to investigate the effects of kindling during pregnancy on long-term potentiation (LTP) induction and the role of M1 muscarinic acetylcholine receptors in the hippocampus of male offspring. Experimental approach: Twenty female Wistar rats were divided into two groups on the 13th day of their gestation (kindled and control; n = 10). Animals in the first group were kindled by i.p. injections of 25 mg/kg body weight pentylenetetrazol every 15 min until seizures occurred and the control group received normal saline. The effect of maternal seizures and perfusion of specific M1 muscarinic receptors antagonist (telenzepine at doses of 0.01, 0.1, and 1 nmol) on the LTP induction of 80 pups were tested at 12 weeks of age by field potential recordings. Findings/Results: The results of the electrophysiological study revealed that recurrent seizures during pregnancy impaired field excitatory postsynaptic potentials (fEPSP)-LTP induction and normal development of M1 muscarinic receptors in the hippocampus of male offspring. Also, the results demonstrated that maternal seizure did not significantly affect the paired-pulse indexes and population spike-LTP in the hippocampus of male offspring. Conclusion and implications: Our study showed that recurrent seizures during pregnancy cause impaired fEPSP-LTP induction and abnormal development of the M1 muscarinic receptor in the hippocampus.

Deferoxamine has the Potential to Improve the COVID-19-Related Inflammatory Response in Diabetic Patients.

The clinical state of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been considered a pandemic disease (COVID-19) that is rapidly spreading worldwide. Despite all global efforts, the only treatment for COVID-19 is supportive care and there has been no efficient treatment to fight this plague. It is confirmed that patients with chronic diseases such as cardiovascular disorder and diabetes; are more vulnerable to COVID-19. In the severe type of COVID-19, laboratory findings showed a remarkably enhanced C-reactive protein, IL-6 serum, Iron, and ferritin, which suggest an inflammatory response. Inflammation results in iron homeostasis imbalance and causes iron overload, exacerbating the SARSCOV2 infection. More importantly, recent studies have established that SARS-CoV-2 needs iron for viral replication and also activation. As a result, managing iron overload in diabetic patients with COVID-19 could be an early therapeutic approach to limit the lethal inflammatory response of COVID-19. In this review, Deferoxamine (DFO) has been proposed as an effective iron chelator agent.

Development of anxiety-like behaviors during adolescence: Persistent effects of adolescent morphine exposure in male rats.

Epidemiological studies show the prevalence of opioid use, misuse and abuse in adolescents, which imposes social and economic accountability worldwide. Chronic opioid exposure, especially in adolescents, may have lasting effects on emotional behaviors that persist into adulthood. The current experiments were therefore designed to study the effects of sustained opioid exposure during adolescence on anxiety-like behaviors. Adolescent male Wistar rats underwent increasing doses of morphine for 10 days (PNDs 31-40). After that the open field test (OFT) and elevated plus maze (EPM) test were performed over a 4-week postmorphine treatment from adolescence to adulthood. Moreover, the weight of the animals was measured at these time points. We found that chronic adolescent morphine exposure reduces the weight gain during the period of morphine treatment and 4 weeks after that. It had no significant effect on the locomotor activity in the animals. Moreover, anxiolytic-like behavior was observed in the rats exposed to morphine during adolescence evaluated by OFT and EPM test. Thus, long-term exposure to morphine during adolescence has the profound potential of altering the anxiety-like behavior profile in the period from adolescence to adulthood. The maturation of the nervous system can be affected by drug abuse during the developmental window of adolescence and these effects may lead to behaviorally stable alterations.

Aerobic training improves blood-brain barrier and neuronal apoptosis in experimental autoimmune encephalomyelitis.

Objectives: Blood-brain barrier (BBB) permeability is central in multiple sclerosis (MS) pathophysiology, and exercise may improve BBB integrity. The current study investigated the prophylactic and/ or therapeutic role of aerobic exercise (EX) training on BBB integrity in experimental autoimmune encephalomyelitis (EAE). Materials and Methods: Forty female Lewis rats were randomly divided into four groups. The experimental groups included: no-EAE induction+ no-exercise (no-EAE+ no-EX), no-EAE induction+ exercise (no-EAE+EX), EAE induction+ no-exercise (EAE+ no-EX), and EAE induction+ exercise (EAE+EX). The no-EAE+EX and EAE+EX groups performed six weeks of progressive aerobic exercise training. GFAP, angiopoietin 1 (Ang-1) expression, tight-junction (TJ) proteins of claudin-5 and occludin were measured as components of BBB integrity and the rate of neuronal apoptosis was evaluated in hippocampi. Results: A significant increase in GFAP and Ang-1 expression (P<0.001) and conversely a down-regulation in TJ proteins (P<0.05) was found in the brains of the no-EAE+EX group compared with the no-EAE+ no-EX group. The expression of GFAP and Ang-1 proteins significantly increased in the hippocampi of the EAE+ no-EX group (P<0.001), whereas aerobic training (in the EAE+EX group) meaningfully reversed such increases (P<0.001). Besides, down-regulated TJ proteins and increased neuronal apoptosis induced by EAE induction (EAE+ no-EX group) were restored and reduced, respectively, by aerobic training in the CNS of the EAE+EX group (P<0.001). Conclusion: The provision of a six-week treadmill aerobic training buffered the detrimental effects of EAE on BBB integrity and consequently neuronal apoptosis.

Impairment of spatial memory and dorsal hippocampal synaptic plasticity in adulthood due to adolescent morphine exposure.

Opioid exposure during adolescence, a crucial period of neurodevelopment, has lasting neurological and behavioral consequences and affects the cognitive functions in adulthood. This study investigated the effects of adolescent morphine exposure in spatial learning and memory and synaptic plasticity of the CA1 area of the dorsal hippocampus. Adolescent Wistar rats received increasing doses of morphine for 1, 5, and 10 days. Acute morphine group was injected 2.5 mg/kg morphine for 1 day, subchronic morphine group for 5 days, with an increasing dose of 2.5 mg/kg and reached to the dose of 12.5 mg/kg and chronic morphine group for 10 days that began with an increasing dose of 2.5 mg/kg and reached to the dose of 25 mg/kg. Then after 25 days and reaching adulthood, spatial learning and memory were evaluated via the Morris water maze (MWM) test. Moreover, we test the electrophysiological properties of dorsal hippocampal plasticity in adult rats by in vitro field potential recordings. Subchronic and chronic adolescent morphine exposure impaired spatial learning and memory in the MWM test. Baseline synaptic responses in the chronic morphine group were increased and long-term potentiation (LTP) impaired in the CA1 area in subchronic and chronic morphine groups. In adulthood, the slope of the field excitatory postsynaptic potential (fEPSP) required to elicit a half-maximal population spike (PS) amplitude was significantly larger in subchronic and chronic adolescent morphine exposure compared to the saline group. Therefore, subchronic and chronic adolescent morphine exposure altered synaptic transmission and plasticity in addition to learning and memory. Long-term morphine exposure during adolescence can interfere with neurodevelopment, making a persistent impression on plasticity and cognitive capability in adulthood.

Tribulus terrestris and female reproductive system health: A comprehensive review.

BACKGROUND: Tribulus terrestris L. (T. terrestris) positive performance on the male sexual system has been confirmed, but little is known about its effects on the female reproductive system. PURPOSE: This review discussed in detail the beneficial impact of T. terrestris and its secondary metabolites on the female reproductive system. STUDY DESIGN AND METHODS: In this review, the scientific Databases of Science direct, Pubmed, Web of Science, Google, Google Scholar, Researchgate, EMBASE, Scientific Information (SID), and Elsevier were searched profoundly. Studies about the pharmacological activities of T. terrestris on the female reproductive system in each aspect of investigations: human, in vivo, and in vitro studies, in the period from 1998 to 2020 were admitted. Our study was not limited by the language of publications. RESULTS: 23 articles about the effects of T. terrestris on the female reproductive system were found. These studies approved the T. terrestris efficacy on improvements in histological features of the ovary and uterus of polycystic ovary syndrome patients as well as the well-working of normal ovaries, enhancements in the sexual desire of postmenopausal syndrome, improve ovarian and breast cancers. CONCLUSION: These studies showed that the positive effect of T. terrestris on the female reproductive system was due to the presence of a secondary metabolite called protodioscin; a steroidal saponin compound, as the dominant active component of this plant.

Acacetin Alleviates Hepatitis Following Renal Ischemia-Reperfusion in Male Balb/C Mice by Antioxidants Regulation and Inflammatory Markers Suppression.

BACKGROUND: Ischemia-reperfusion (Isc/Rep) incidence can damage kidneys and long-distance organs such as the liver. Due to the increasing use of herbs in medicine, this study was designed to assess the effects of Acacetin (ACA) on pathophysiology of liver following renal Isc/Rep induction. Methods: 84 male Balb/C mice were divided into 12 groups including control, control + ACAs groups (0.01% DMSO or 50, 25, 10 mg/kg of ACA.) sham group (a period of 60 min laparotomy with 0.01% DMSO treatment) sham + ACAs groups (0.01% DMSO + 50, 25, 10 mg/kg of ACA) Isc/Rep treatment groups (laparotomy and bilateralrenal occlusion for 60 min with/without administration of 50, 25, 10 mg/kg ACA). All experimental groups were treated intraperitoneally daily for 4 consecutive days. The values of quantitative histology, Total Antioxidant Capacity (TAC), Nitric oxide (NO), TNFα, IL1ß, and the serum levels of hepatic enzymes were evaluated. Results: In the Isc/Rep and Isc/Rep + ACA (10 mg/kg) groups, there were a significant decrease in the level of albumin and TAC, while the other evaluated parameters were significantly increased (p < 0.05). In the Isc/Rep + ACA (25, 50 mg/kg), these parameters showed significant recovery compared to Isc/Rep + ACA (10 mg/kg) group (p < 0.05). Conclusion: Increasing the oxidant activity is the most important cause of injury in long-distance organs following Isc/Rep process. By employing the inflammatory mediators in a dose-dependent manner, the ACA reveals the recovery effects on liver failure.

Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.

The current study was designed to examine the involvement of cannabinoid CB1 receptors in the basolateral amygdala (BLA) in scopolamine-induced memory impairment in adult male Wistar rats. The animals were bilaterally implanted with the cannulas in the BLA and submitted to a step-through type passive avoidance task to measure the memory formation. The results showed that intraperitoneal (i.p.) administration of different doses of scopolamine (0.5-1.5mg/kg) immediately after the training phase (post-training) impaired memory consolidation. Bilateral microinjection of the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA; 1-4ng/rat), into the BLA significantly improved scopolamine-induced memory consolidation impairment. On the other hand, co-administration of AM251, a cannabinoid CB1 receptor antagonist (0.25-1ng/rat, intra-BLA), with an ineffective dose of scopolamine (0.5mg/kg, i.p.), significantly impaired memory consolidation and mimicked the response of a higher dose of scopolamine. It is important to note that post-training intra-BLA microinjections of the same doses of ACPA or AM251 alone had no effect on memory consolidation. Moreover, the blockade of the BLA CB1 receptors by 0.3ng/rat of AM251 prevented ACPA-induced improvement of the scopolamine response. In view of the known actions of the drugs used, the present data pointed to the involvement of the BLA CB1 receptors in scopolamine-induced memory consolidation impairment. Furthermore, it seems that a functional interaction between the BLA endocannabinoid and cholinergic muscarinic systems may be critical for memory formation.

Effects of Peripheral and Intra-hippocampal Administration of Sodium Salicylate on Spatial Learning and Memory of Rats.

OBJECTIVES: Cyclooxygenases (COXs) are known to play some roles in physiological mechanisms related to learning and memory. Since sodium salicylate is an inhibitor of COX, we have evaluated the effect of peripheral and intra-hippocampal administration of sodium salicylate on spatial learning and memory in male rats. MATERIALS AND METHODS: Male rats were studied in two groups; the first group received different intraperitoneal (i.p.) sodium salicylate doses (0, 200, 300, and 400 mg/kg) and the second group received intra-hippocampal doses of the drug (0, 30, 50, and 100 µg/0.5 µl/side). The spatial performance of rats was tested using Morris water maze (MWM) task. The spatial learning and memory parameters were analyzed using ANOVA. RESULTS: Peripheral and intra-hippocampal administration of sodium salicylate did not lead to a statistically significant change in the mean time (escape latency), and also the distance traveled for finding the hidden platform during the training days, compared with the control group. But at the probe trial, the percentage of time spent in the target quadrant by rats which received the highest doses of drug significantly increased. CONCLUSION: We found that both peripheral and intra-hippocampal administration of sodium salicylate facilitates the process of spatial memory consolidation in the MWM.