An overview of pharmacological effects of Crocus sativous and its constituents.

Crocus sativus L. was used for the treatment of a wide range of disorders in traditional medicine. Due to the extensive protective and treatment properties of C. sativus and its constituents in various diseases, the purpose of this review is to collect a summary of its effects, on experimental studies, both in vitro and in vivo. Databases such as PubMed, Science Direct, and Scopus were explored until January 2023 by employing suitable keywords. Several investigations have indicated that the therapeutic properties of C. sativus may be due to its anti-oxidant and anti-inflammatory effects on the nervous, cardiovascular, immune, and respiratory systems. Further research has shown that its petals also have anticonvulsant properties. Pharmacological studies have shown that crocetin and safranal have anti-oxidant properties and through inhibiting the release of free radicals lead to the prevention of disorders such as tumor cell proliferation, atherosclerosis, hepatotoxicity, bladder toxicity, and ethanol induced hippocampal disorders. Numerous studies have been performed on the effect of C. sativus and its constituents in laboratory animal models under in vitro and in vivo conditions on various disorders. This is necessary but not enough and more clinical trials are needed to investigate unknown aspects of the therapeutic properties of C. sativus and its main constituents in different disorders.

Feasibility Study of Convolutional Long ShortTerm Memory Network for Pulmonary Movement Prediction in CT Images.

Background: During X-ray imaging, pulmonary movements can cause many image artifacts. To tackle this issue, several studies, including mathematical algorithms and 2D-3D image registration methods, have been presented. Recently, the application of deep artificial neural networks has been considered for image generation and prediction. Objective: In this study, a convolutional long short-term memory (ConvLSTM) neural network is used to predict spatiotemporal 4DCT images. Material and Methods: In this analytical analysis study, two ConvLSTM structures, consisting of stacked ConvLSTM models along with the hyperparameter optimizer algorithm and a new design of the ConvLSTM model are proposed. The hyperparameter optimizer algorithm in the conventional ConvLSTM includes the number of layers, number of filters, kernel size, epoch number, optimizer, and learning rate. The two ConvLSTM structures were also evaluated through six experiments based on Root Mean Square Error (RMSE) and structural similarity index (SSIM). Results: Comparing the two networks demonstrates that the new design of the ConvLSTM network is faster, more accurate, and more reliable in comparison to the tuned-stacked ConvLSTM model. For all patients, the estimated RMSE and SSIM were 3.17 and 0.988, respectively, and a significant improvement can be observed in comparison to the previous studies. Conclusion: Overall, the results of the new design of the ConvLSTM network show excellent performances in terms of RMSE and SSIM. Also, the generated CT images with the new design of the ConvLSTM model show a good consistency with the corresponding references regarding registration accuracy and robustness.

Ionic and nanoparticulate silver alleviate the toxicity of inorganic mercury in marine microalga Chaetoceros muelleri.

Toxicological effects of silver nanoparticles (SNPs) in different organisms have been studied; however, interactions of SNPs with other environmental pollutants such as mercury are poorly understood. Herein, bioassay tests were performed according to ΟECD 201 guideline to assess the toxic effects induced by mercury ions (mercury chloride, MCl) on the marine microalga Chaetoceros muelleri in the presence of SNPs or silver ions (silver nitrate, SN). Acute toxicity tests displayed that the presence of SNPs or SN (0.01 mg L-1) significantly reduced the toxicity of MCl (0.001, 0.01, 0.1, 1, 10, and 100 mg L-1) and increased the IC50 of MCl from 0.072 ± 0.014 to 0.381 ± 0.029 and 0.676 ± 0.034 mg L-1, respectively. In the presence of SN or SNPs, the mercury-reducing effect on algal population growth significantly decreased. Considering the increase of IC50, the mercury toxicity decreased approximately 5.44 and 9.66 times in the presence of SNPs or SN, respectively. The chlorophyll a and c contents decreased at all exposures; however, the decrease by MCl-SNPs and MCl-SN was significantly less than MCl except at 1 mg L-1. The lowering effect of MCl-SN on chlorophyll contents was less than MCl and MCl-SNPs. MCl exposure induced significant raises in total protein content (TPC) at concentrations < 0.01mg  L-1, with a maximum of ~ 70.83% attained at 100 mg L-1. The effects of MCl-SNPs and MCl-SN on TPC were significantly less than MCl. Total lipid content (TLC) at all MCl concentrations was higher than the control, while at coexposure to MCl-SN, TLC did not change until 0.01 mg L-1 compared with the control. The effects of MCl-SN and MCL-SNPs on TPC and TLC were in line with toxicity results, and were significantly less than those of MCl individually, confirming their antagonistic effects on MCl. The morphological changes of algal cells and mercury content of the cell wall at MCl-SN and MCl-SNPs were mitigated compared with MCl exposure. These findings highlight the mitigatory impacts of silver species on mercury toxicity, emphasizing the need for better realizing the mixture toxicity effects of pollutants in the water ecosystem.

Efficient oxidation of sulfides to sulfoxides catalyzed by heterogeneous Zr-containing polyoxometalate grafted on graphene oxide.

In this study, a tri-component composite named Zr/SiW12/GO was meticulously prepared through an ultrasonic-assisted method. This composite incorporates zirconium nanoparticles (Lewis acid), a negatively charged Keggin type polyoxometalate, and graphene oxide, and serves as a remarkable heterogeneous catalyst. The Keggin component plays multiple roles as reducing, encapsulating, and bridging agents, resulting in a cooperative effect among the three components that significantly enhances the catalytic activity. The catalytic performance of Zr/SiW12/GO was thoroughly investigated in the oxidation of sulfides to sulfoxides under mild conditions, employing H2O2 as the oxidant. Remarkably, this composite exhibited exceptional stability and could be effortlessly recovered and reused up to four times without any noticeable loss in its catalytic activity.

Toxicological Impacts of TiO2 Nanoparticles on Growth, Photosynthesis Pigments, and Protein and Lipid Content of the Marine Microalga Tetraselmis Suecica.

Regarding the widespread use of titanium dioxide nanoparticles (TiO2NPs) in industry, many concerns have been raised about the risks of their potential release into aquatic ecosystems. Among the marine primary producers, Tetraselmis suecica is an ecologically important microalgae species used also as live feed in the shrimp culture industry. In the present study, the impacts of TiO2NPs on growth performance, photosynthetic pigments, lipid and protein content and its interaction with the cells of T. suecica were assessed. Based on the preliminary tests and OECD suggestion, concentrations of 5, 10, 50, 100, 200 and 400 mg/L TiO2NPs were applied to algal cells for 10 days. With increasing concentration, a decrease in T. suecica cell density was observed each day. TiO2NPs induced a half-maximal inhibitory concentration (IC50) of 106.26 mg/L on algal cells on the 3rd day. Chlorophyll a and b contents of the microalga decreased up to 56.08% and 52.74%, respectively following the exposure to TiO2NPs at 400 mg/L. TiO2NPs also decreased the algal contents of protein and lipid up to 7.21% and 50.64%, respectively at the highest concentration. Based on FTIR, FESEM with EDS and mapping analyses, the interaction of TiO2NPs with the T. suecica cells was revealed. The stocks of T. suecica could be damaged by the toxic effects of the released TiO2NPs affecting their application as live feed in mariculture.

Current status of nano-vaccinology in veterinary medicine science.

Vaccination programmes provide a safe, effective and cost-efficient strategy for maintaining population health. In veterinary medicine, vaccination not only reduces disease within animal populations but also serves to enhance public health by targeting zoonoses. Nevertheless, for many pathogens, an effective vaccine remains elusive. Recently, nanovaccines have proved to be successful for various infectious and non-infectious diseases of animals. These novel technologies, such as virus-like particles, self-assembling proteins, polymeric nanoparticles, liposomes and virosomes, offer great potential for solving many of the vaccine production challenges. Their benefits include low immunotoxicity, antigen stability, enhanced immunogenicity, flexibility sustained release and the ability to evoke both humoral and cellular immune responses. Nanovaccines are more efficient than traditional vaccines due to ease of control and plasticity in their physio-chemical properties. They use a highly targeted immunological approach which can provide strong and long-lasting immunity. This article reviews the currently available nanovaccine technology and considers its utility for both infectious diseases and non-infectious diseases such as auto-immunity and cancer. Future research opportunities and application challenges from bench to clinical usage are also discussed.

Neurostimulation as a Putative Method for the Treatment of Drug-resistant Epilepsy in Patient and Animal Models of Epilepsy.

A patient with epilepsy was shown to have neurobiological, psychological, cognitive, and social issues as a result of recurring seizures, which is regarded as a chronic brain disease. However, despite numerous drug treatments, approximately, 30%-40% of all patients are resistant to antiepileptic drugs. Therefore, newer therapeutic modalities are introduced into clinical practice which involve neurostimulation and direct stimulation of the brain. Hence, we review published literature on vagus nerve stimulation, trigeminal nerve stimulation, applying responsive stimulation systems, and deep brain stimulation (DBS) in animals and epileptic patient with an emphasis on drug-resistant epilepsy.

High and Low-Frequency Stimulation Effect on Epileptiform Activity in Brain Slices.

Background: Neurostimulation is one of the new therapeutic approaches in patients with drug-resistant epilepsy, and despite its high efficiency, its mechanism of action is still unclear. On the one hand, electrical stimulation in the human brain is immoral; on the other hand, the creation of the epilepsy model in laboratory animals affects the entire brain network. As a result, one of the ways to achieve the neurostimulation mechanism is to use epileptiform activity models In vitro. In vitro models, by accessing the local network from the whole brain, we can understand the mechanisms of action of neurostimulation. Methods: A literature search using scientific databases including PubMed, Google Scholar, and Scopus, using "Neurostimulation" and "epileptiform activity" combined with "high-frequency stimulation", " low-frequency stimulation ", and "brain slices" as keywords were conducted, related concepts to the topic gathered and are used in this paper. Results: Electrical stimulation causes neuronal depolarization and the release of GABAA, which inhibits neuronal firing. Also, electrical stimulation inhibits the nervous tissue downstream of the stimulation site by preventing the passage of nervous activity from the upstream to the downstream of the axon. Conclusion: Neurostimulation techniques consisting of LFS and HFS have a potential role in treating epileptiform activity, with some studies having positive results. Further investigations with larger sample sizes and standardized outcome measures can be conducted to validate the results of previous studies.

MiR-548 K regulatory effect on the ABCG2 gene expression in MDR breast cancer cells.

BACKGROUND: multidrug resistance (MDR) is One of the foremost challenges in overcoming breast cancer. Various molecular processes are involved in the development of MDR in breast cancer cells, including over expression of ABC transporters such as ABCG2 (BCRP), increase breast cancer stem cells drug resistance, and epithelial mesenchymal transition. AIMS: In the present study, we used bioinformatics and experimental analysis to investigate the role of miR-548 K, in the modulating of ABCG2, in MDR breast cancer cells. METHODS AND RESULTS: In silico inspections introduce 14 microRNAs targeting 3'-UTR region of ABCG2 transcripts, which are probably involved in breast cancer drug resistance. An association was highlighted between miR-548 k with ABC transporter family. The expression level of ABCG2 gene in MCF7-MX cell lines was significantly more than MCF7 cell lines. On the other hand, we increased the expression of miR-548 K in MCF7-MX and MCF7 cell lines through its transfection, which dramatically coincided with decreasion in the ABCG2 transcripts level. Additional studies on patient samples revealed that the expression of ABCG2 showed an increase in ABCG2 level in neoadjuvant chemotherapy drugs resistance (NCDR) patients compared to primary pre-operative chemotherapy drugs response (PCDR) patients. Also, a reduction in the expression of miR-548 K in NCDR patients was revealed. CONCLUSION: The results of our study suggest that miR-548 K may be involved in modulating the expression of ABCG2 in MDR breast cancer cells.

Alpha adrenergic receptors have role in the inhibitory effect of electrical low frequency stimulation on epileptiform activity in rats.

Aim: Low frequency stimulation (LFS) inhibits neuronal hyperexcitability following epileptic activity. However, knowledge about LFS' inhibitory mechanisms is lacking. Here, α1 and α2 adrenergic receptors' roles in mediating LFS inhibitory action on high-K+ induced epileptiform activity (EA) was examined in rat hippocampal slices.Materials and methods: LFS (1 Hz, 900 pulses) was applied to the Schaffer collaterals. Whole-cell, patch clamp recording was used to measure changes in CA1 pyramidal neurons' excitability. By applying high-K+ on hippocampal slices, EA was induced, and neuronal excitability increased.Results: When administered at the beginning of EA, LFS reduced neuronal excitability. In the presence of prazosin (10 µM, an α1 adrenergic receptor antagonist) and yohimbine (5 µM, an α2 adrenergic receptor antagonist), LFS' typically has a restorative impact on EA-induced membrane potential hyperpolarization and spike firing frequency, but this effect was reduced after high-K+ washout; These antagonists did not have a significant effect on LFS' inhibitory action on spike firing during EA.Conclusion: These findings suggest that LFS' anticonvulsant effect, on neuronal hyperexcitability following high-K+ EA, may be mediated partly through α adrenergic receptors in hippocampal slices.

Non-coding RNAs and epithelial mesenchymal transition in cancer: molecular mechanisms and clinical implications.

Epithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer malignant features to carcinoma cells such as dissemination throughout the organism and resistance to anticancer treatments. During the past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized as a key regulator of almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting as oncogenes or tumor suppressors. The various forms of ncRNAs, including microRNAs, PIWI-interacting RNAs, small nucleolar RNAs, transfer RNA-derived RNA fragments, long non-coding RNAs, and circular RNAs can orchestrate the complex regulatory networks of EMT at multiple levels. Understanding the molecular mechanism underlying ncRNAs in EMT can provide fundamental insights into cancer metastasis and may lead to novel therapeutic approaches. In this review, we describe recent advances in the understanding of ncRNAs in EMT and provide an overview of recent ncRNA applications in the clinic.

Incorporating heterogeneous lacunary Keggin anions as efficient catalysts for solvent-free cyanosilylation of aldehydes and ketones.

Polyoxometalates (POMs) as efficient catalysts can be used a wide range of chemical transformations due to their tunable Brønsted/Lewis-acidity and redox properties. Herein, we reported two hybrid and heterogeneous lacunary Keggin catalysts: (TBA)7[PW11O39] (TBA-PW11) and (TBA)8[SiW11O39]·4H2O (TBA-SiW11) (TBA+: tetrabutylammonium) in which [XW11O39]n- anions were coated by TBA+ cations. In this form, TBA+ can easily trap reactants on the surface of the catalysts and increase the catalytic reaction. Therefore, the catalytic performance of both POMs was tested in cyanosilylation of numerous compounds bearing-carbonyl group and trimethylsilyl cyanide under solvent-free conditions. TBA-PW11 is more effective than TBA-SiW11, conceivably due to the higher Lewis acidity of the P than the Si center and to the higher accessibility of the metal centers in the framework structure. Noteworthy, the recyclability and heterogeneity of both POMs catalysts were also examined, and the results confirmed that they remain active at least after three recycling procedures.

A Review of Recent Advances in Natural Polymer-Based Scaffolds for Musculoskeletal Tissue Engineering.

The musculoskeletal (MS) system consists of bone, cartilage, tendon, ligament, and skeletal muscle, which forms the basic framework of the human body. This system plays a vital role in appropriate body functions, including movement, the protection of internal organs, support, hematopoiesis, and postural stability. Therefore, it is understandable that the damage or loss of MS tissues significantly reduces the quality of life and limits mobility. Tissue engineering and its applications in the healthcare industry have been rapidly growing over the past few decades. Tissue engineering has made significant contributions toward developing new therapeutic strategies for the treatment of MS defects and relevant disease. Among various biomaterials used for tissue engineering, natural polymers offer superior properties that promote optimal cell interaction and desired biological function. Natural polymers have similarity with the native ECM, including enzymatic degradation, bio-resorb and non-toxic degradation products, ability to conjugate with various agents, and high chemical versatility, biocompatibility, and bioactivity that promote optimal cell interaction and desired biological functions. This review summarizes recent advances in applying natural-based scaffolds for musculoskeletal tissue engineering.

Toxicity of TiO2 nanoparticles to the marine microalga Chaetoceros muelleri Lemmermann, 1898 under long-term exposure.

Titanium dioxide nanoparticles (TiO2NPs) have been extensively used in industry, raising many concerns about their release into the aquatic environments. In marine ecosystems, microalgae are major primary producers; among them, Chaetoceros muelleri is an important microalga in the aquaculture industry as live feed. The impacts of TiO2NPs on the growth, photosynthetic pigments, protein and lipid contents, and the interaction of TiO2NPs with the cell wall of C. muelleri were investigated in the present study. Algal cells were exposed to concentrations of 5, 10, 50, 100, 200, and 400 mg/L TiO2NPs for 10 days. There was a significant difference in the growth between the control and TiO2NPs treatments on each day. The half-maximal inhibitory concentration (IC50) of TiO2NPs on algal cells was found to be 10.08 and 5.01 mg/L on the 3rd and 10th days, respectively. The contents of chlorophyll a and c reduced significantly in the TiO2NPs-treated microalgae. TiO2NPs also reduced the protein and lipid contents in the treated microalgae, up to 13.02% and 47.6% respectively, at the highest concentration. The interaction of TiO2NPs with the C. muelleri cells was obvious based on Fourier transform infrared spectroscopy, microscopic images, EDS, and Mapping analyses. Toxic effects of the released TiO2NPs can damage the stocks of C. muelleri as an important live feed in mariculture.

ESRG, LINC00518 and PWRN1 are newly-identified deregulated lncRNAs in colorectal cancer.

Colorectal cancer is the 2nd leading cause of death in humans because of cancer. This rank of death could be due to the high rate of incidence from one hand, and the lack of sufficient diagnostic and therapeutic approaches from the other hand. Thus, molecular tools have been emerging as the potential biomarker to improve the early diagnosis and therapeutic management that subsequently could lead to the heightened survival rate of colorectal cancer patients. Long non-coding RNA (lncRNAs) have shown promising capabilities to be used in clinics. The profiling methods could identify novel aberrantly expressed lncRNAs in colorectal cancer. We, thus, performed a comprehensive and unbiased approach to shortlist the dysregulated lncRNAs based on the colon adenocarcinoma TCGA data. An unbiased in silico method was used to rank the yet to profiled lncRNAs in colorectal cancer. qPCR was used to measure the expression level of selected lncRNAs. Our results nominated ESRG, LINC00518, PWRN1, and TTTY14 lncRNAs as the top-hit novel lncRNAs with aberrant expression in colon cancer. The qPCR method was used to profile these lncRNAs that showed the up-regulation of ESRG and LINC00518, and down-regulation of TTTY14 in thirty paired colorectal cancer specimens. The statistical analyses demonstrated that ESRG, LINC00518 and PWRN1 could distinguish the tumor from normal samples. Moreover, ESRG showed a negative correlation with the overall survival of patients. These diagnostic and prognostic results suggest that profiling ESRG, LINC00518 and PWRN1 s may have implications in clinics.

Group I metabotropic glutamate receptors contribute to the antiepileptic effect of electrical stimulation in hippocampal CA1 pyramidal neurons.

Low-frequency deep brain stimulation (LFS) inhibits neuronal hyperexcitability during epilepsy. Accordingly, the use of LFS as a treatment method for patients with drug-resistant epilepsy has been proposed. However, the LFS antiepileptic mechanisms are not fully understood. Here, the role of metabotropic glutamate receptors group I (mGluR I) in LFS inhibitory action on epileptiform activity (EA) was investigated. EA was induced by increasing the K+ concentration in artificial cerebrospinal fluid (ACSF) up to 12 mM in hippocampal slices of male Wistar rats. LFS (1 Hz, 900 pulses) was delivered to the bundles of Schaffer collaterals at the beginning of EA. The excitability of CA1 pyramidal neurons was assayed by intracellular whole-cell recording. Applying LFS reduced the firing frequency during EA and substantially moved the membrane potential toward repolarization after a high-K+ ACSF washout. In addition, LFS attenuated the EA-generated neuronal hyperexcitability. A blockade of both mGluR 1 and mGluR 5 prevented the inhibitory action of LFS on EA-generated neuronal hyperexcitability. Activation of mGluR I mimicked the LFS effects and had similar inhibitory action on excitability of CA1 pyramidal neurons following EA. However, mGluR I agonist's antiepileptic action was not as strong as LFS. The observed LFS effects were significantly attenuated in the presence of a PKC inhibitor. Altogether, the LFS' inhibitory action on neuronal hyperexcitability following EA relies, in part, on the activity of mGluR I and a PKC-related signaling pathway.

The Effect of Peer Support on Foot Care in Patients with Type 2 Diabetes.

BACKGROUND: Diabetes mellitus is one of the prevalent diseases in the world with several complications including diabetic foot ulcers. The aim of this study was to investigate the effect of peer support on foot care in patients with type 2 diabetes. MATERIALS AND METHODS: This clinical trial study was performed at selected centers of Isfahan University of Medical Sciences in 2017. Fifty patients with type 2 diabetes were randomly assigned into intervention and control groups. Five 30-min. supportive training sessions were held for the intervention group by the peers and during 35 days. Foot Care Confidence/Foot-Care Behavior Scale For Diabetes (FCCS-FCB) was completed by both groups before, immediately after and 1 month after the intervention. Collected data were analyzed using Chi-square, Mann-Whitney, repeated measures ANOVA and t-test. RESULTS: : Mean (SD) age of subjects was 56.46 (7.36) years old Mean (SD) score of self-efficacy (F2, 26 = 54.71, p < 0.001), preventive behaviors (F2, 26 = 28.46, p < 0.001), and potentially damaging (F2, 26 = 27.89, p < 0.001) had significant differences between the two groups immediately and 1 month after the peer support. CONCLUSIONS: Peer support can enhance foot care behaviors in diabetic patients. Therefore, using people who are successful in the education and support of patients has a significant role, and nurses can use them as a support in the field of care and follow-up. However, health agencies are responsible for providing the patients with the best guidelines, and these results can be useful as an evidence for them.

Association of maternal exposure to bisphenol A with her ß-hCG level and neonatal anthropometric measures.

Bisphenol A (BPA) is one of the organic compounds that might interfere with estrogenic receptors, which would make difficulties in pregnancy hormones and fetal growth. Human chorionic gonadotropin (ß-hCG) is one of the important pregnancy hormones that might be affected by environmental pollutants. The aim of this study is to investigate the probable impacts of maternal exposure to BPA on anthropometric measures of newborns. This cross-sectional study was conducted in 2019-2020 in Isfahan, Iran. During the first trimester of pregnancy, we measured the urinary BPA concentration and serum ß-hCG level of 120 pregnant women, who were randomly selected from participants of a birth cohort. BPA concentration was measured using gas chromatography-mass spectrometry (GC-MS). Serum blood sample was derived and used for ß-hCG analysis. Anthropometric measurement of neonates was conducted at the time of birth. BPA and ß-hCG level were grouped by quartiles, and their associations with birth weight, height, and head circumference were tested using multiple linear regression model. The adjustment was done for urine creatinine, gender, and gestational age, as well as maternal age, body mass index, and education level. Data of 119 pairs of mothers and infants were available for the present study. The mean (SD) age of mothers was 29.19 (5.75) years; 56.3% of newborns were boys. Geometric mean of urinary BPA and ß-hCG concentrations were 0.36 ng/g crea. (creatinine) and 17736 mIU/ml, respectively. Across the BPA tertiles, the differences in mean values were not significant for none of the anthropometric measurements and gestational age (GA). Furthermore, no significant association existed between unadjusted and adjusted tertiles of BPA and ß-hCG with abovementioned birth outcomes. It seems that the non-significant association found in this study is because of low levels of urinary BPA levels than in other studies; the adverse effects on infants might be related to high concentration of BPA passed from placenta. Future longitudinal studies with large sample size are necessary to document the adverse health effects of maternal exposure to endocrine disruptor chemicals including BPA.

5-HT7 receptor activation rescues impaired synaptic plasticity in an autistic-like rat model induced by prenatal VPA exposure.

Autism spectrum disorder (ASD) is a severe life-long neuropsychiatric disorder. Alterations and imbalance of several neurochemical systems may be involved in ASD pathophysiology, of them, serotonergic neurotransmission dysfunction and deficiency may underlie behavioral abnormalities associated with ASD. However, the functional importance of serotonergic receptors, particularly 5HT7 receptors in ASD pathology remains poorly defined. Serotonin receptor subtype 7 (5-HT7R) plays a direct regulatory role in the development and also for the mature function of the brain, therefore, further studies are necessary to elucidate the role of these receptors in the etiology of autism. To address this issue, we combined here behavioral, electrophysiological methods to further characterize the contribution of 5-HT7Rs in the prenatal valproic acid (VPA) exposure-induced impairment in synaptic plasticity and their impact on the associated behavioral changes. This may help to unravel the underlying cellular mechanisms involved in ASD and can lead to new treatment and/or prevention therapies based on the role of the serotonergic system for autism. Findings revealed that compared to control, autistic-like offspring showed increased anxiety-like behavior, reduced social interaction, decreased locomotor activity, and impaired identification of the novel object. However, administration of 5-HT7Rs agonist, LP-211, for 7 consecutive days before testing from postnatal day 21 to 27 reversed all behavioral deficits induced by prenatal exposure to VPA in offspring. Also, both short-term depression and long-term potentiation were impaired in the autistic-like pups, but activation of 5-HT7Rs rescued the LTP impairment in the autistic-like group so that there was no significant difference between the two groups. Blockade of 5-HT7Rs caused LTP impairment following HFS in the autistic-like group. Besides, there was a significant difference in LTD induction following SB-269970 application between the control and the autistic-like groups measured at first 10 min following TPS. Moreover, both the number and the size of retrograde fast blue-labelled neurons in the raphe nuclei were reduced. Overall, these results provide for the first time, as far as we know, functional evidence for the restorative role of 5-HT7Rs activation against prenatal VPA exposure induced behavioral deficits and hippocampal synaptic plasticity impairment. Therefore, these receptors could be a potential and promising pharmacotherapy target for the treatment of autism.

The role of α adrenergic receptors in mediating the inhibitory effect of electrical brain stimulation on epileptiform activity in rat hippocampal slices.

The Inhibitory effect of electrical low-frequency stimulation (LFS) on neuronal excitability and seizure occurrence has been indicated in experimental models, but the precise mechanism has not established. This investigation was intended to figure out the role of α1 and α2 adrenergic receptors in LFS' inhibitory effect on neuronal excitability. Epileptiform activity induced in an in vitro rat hippocampal slice preparation by high K+ ACSF and LFS (900 square wave pulses at 1 Hz) was administered at the beginning of epileptiform activity to the Schaffer collaterals. In CA1 pyramidal neurons, the electrophysiological properties were measured at the baseline, before high K+ ACSF washout, and at 15 min after high K+ ACSF washout using whole-cell, patch-clamp recording. Results indicated that after high K+ ACSF washout, prazosine (10 µM; α1 adrenergic receptor antagonist) and yohimbine (5 µM; α2 adrenergic receptor antagonist) suppressed the LFS' effect of reducing rheobase current and utilization time following depolarizing ramp current, the latency to the first spike following a depolarizing current and latency to the first rebound action potential following hyperpolarizing current pulses. Thus, it may be proposed that LFS' inhibitory action on the neuronal hyperexcitability, in some way, is mediated by α1 and α2 adrenergic receptors.