Smartphone-assisted quantitative colorimetric identification of thrombin based on peroxidase mimetic features of fibrinogen-gold nanozymes.

Fibrinogen-modified gold nanoparticles (Fib-AuNPs) and 3,3',5,5'-tetramethylbenzidine (TMB) substrate besides hydrogen peroxide (H2O2) were applied for assessment of the biomarker thrombin. Fib-AuNPs have catalytic active sites for the oxidation of TMB besides H2O2 and cause the color change of the substrate. Moreover, they can lead to the enhancement in the absorption wavelengths of 650 and 370 nm. By the addition of thrombin to Fib-AuNPs, fibrinogen turns into fibrin, and AuNPs are surrounded by fibrin. Therefore, their active catalytic sites for the oxidation of TMB besides H2O2 are covered by fibrin and cannot cause color change and absorption increase as before. The relationship between the average variations of the color intensity and changes in the absorption wavelengths at 650 and 350 nm with different concentrations of bovine thrombin added to Fib-AuNPs was studied. In such manner, three sensitive colorimetric approaches have been developed for the identification of bovine thrombin with the linear range of 20-120 pM and the limit of detection (LOD) of 17.54 pM for the average color intensity (G + B), the linear range of 20-120 pM and the LOD of 13.41 pM for the absorption peak at 650 nm, and the linear range of 40-140 pM with the LOD of 18.85 pM for absorption peak at 370 nm. The practical application of this biosensing platform was indicated through the successful determination of bovine thrombin in bovine serum. The satisfactory RSD ( < 10%) and recovery values (99.11-107.61%) confirmed the feasibility of the fabricated sensor.

Clinical manifestations of pain in patients suffering from COVID-19 infected with Delta variant of SARS-Cov-2.

Background: Although respiratory presentations of COVID-19 predominate, the extra pulmonary involvement such as muscle pain, joint pain, headache, back pain, abdominal pain, and sore throat are usually included in the clinical picture of the disease and it can be considered as an early symptom in COVID-19 patients. The objective of the present study was to determine the frequency, localization, and intensity of pain in COVID-19 patients hospitalized in Imam Khomeini hospital of Ardabil, Iran. Methods and materials: A prospective study was conducted on 388 COVID-19 patients who were admitted to Ardabil, Iran's Imam Khomeini Central Hospital between March and June 2020. Demographic characteristics of patients and general clinical manifestations of pain at the first admission to the hospital, localization, severity, and continuity of pain were evaluated by using a questionnaire and the Visual Analog Scale (VAS). Findings: For the 388 (51.3% female, age 47.25 + 15.55 and 48.7% male, age 50.12 + 15.26 years old) Delta COVID-19 patients, the median duration from illness onset to hospitalization was 5 days. Patients' complaints included 89.7% fatigue, 85.56% cough, 67.8% fever, 64.17% loss of taste, 63.91% loss of smell, 37.9% diarrhea, and 11.85% skin lesions, respectively. Pain including muscle, joint, bone and low back pain was the chief complaint in both sexes. Pain complaints had started on average 5 days before admission. The distribution of pain was 313 (80.41%) muscle pain, 264 (70.61%) joint pain, 299 (77.1%) headache, 208 (53.6%) low back pain, 312 (80.41%) sore throat, and 157 (40.46%) abdominal pain. Out of 388 patients, 292 (75.25%) had diffuse pain. Conclusions: Acute pain including myalgia, sore throat, arthralgia, headache, and low back pain were the most common symptoms of COVID-19 patients. Viral diseases such as COVID-19 may trigger the immune system to release cytokines that lead to muscle pain. Patients presenting to healthcare centers with complaints of pain should be evaluated for suspected COVID-19 infection.

Colorectal Cancer Screening Pilot Project in Tehran-Iran, a Feasibility Study.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in Iran, where there is no organised CRC-screening programme. This study aimed to evaluate feasibility of CRC screening using a qualitative fecal immunochemical test (FIT) among Iranian average-risk adults. METHODS: In this feasibility study, 7039 individuals aged 50-75 years were invited by community health workers (CHWs) in southern Tehran and its suburban districts between April 2018 and November 2019. The CHWs performed a qualitative FIT with cut-off level 50 ng Hb/mL buffer and referred those with positive-FIT for colonoscopy to the endoscopy center of Shariati hospital in Tehran. Outcomes included acceptance rate, FIT positivity rate, colonoscopy compliance, detection rates and positive predictive values (PPVs) with 95% confidence interval for CRC and advanced adenomas (AAs). RESULTS: Acceptance rate at initial invitation was 71.7%. From 4974 average-risk adults (1600 males and 3374 females) who were offered FIT, 96.8% (n=4813) provided valid samples, of whom 471 (9.8%) tested positive. Among FIT-positive participants, 150 (31.8%) underwent colonoscopy; CRC was detected in 2.0% (n=3) and adenomas in 27.3% (n=41). Detection rate of CRC and AAs per 1000-FIT-screened participants was 0.6 (0.1-1.8) [males: 0.7 (0.01-3.6), females: 0.6 (0.07-2.0)] and 4.2 (2.5-6.4) [males: 5.9 (2.6-11.0), females: 3.4 (1.7-6.0)], respectively. PPVs were 2.0% (0.4-5.7) for CRC and 13.3% (8.3-19.8) for AAs. There was no association between gender and the studied outcomes. CONCLUSION: Our results partially support the feasibility of scaling up organized CRC-screening through the existing healthcare system in Iran; it remains to be discussed carefully to ensure the capacity of healthcare system for adequate colonoscopy services.

Design of an S-scheme photo-catalyst utilizing a Cu-doped perovskite and MOF-5 for simultaneous degradation of organic pollutants under LED light irradiation: Application of EXRSM method for spectra separation and BBD-RSM modeling.

Heterojunction photo-catalysts have attracted significant attention in solar energy conversion due to their ability to reduce suppressing electron-hole pairs and improve catalytic capability. Herein, we designed an S-scheme photo-catalyst by encapsulating a Cu-doped perovskite inside the pores of MOF-5 for the first time, exhibiting excellent efficiency in a pollutant degradation process. The pristine MOF cannot act in the visible light region because of its wide bandgap. However, the encapsulation modified its bandgap and but also increased its photo-catalytic activity. Simultaneous photo-degradation of two organic contaminants, methylene blue (MB) and paracetamol (PA), was investigated to evaluate the catalytic activity of this composite. As a challenge, the UV-vis spectra of PA strongly overlapped with MB in a binary mixture preventing direct measurement of its concentration without previous separation via conventional methodologies. Hence, we used a simple and fast technique called the extended ratio subtraction method (EXRSM) to separate their absorption spectra. The statistical investigations established that it could resolve the issue of signal overlapping. Also, a statistical approach, Box-Behnken (BBD-RSM), was used to model and optimize the degradation process providing a better way to explain the effect and interactions of main parameters on degradation efficiency. Now, an empirical model for each pollutant can make a relationship between them. The photo-degradation yield was obtained at 67.12% and 87.96% for PA and MB, respectively, under optimum conditions. Furthermore, the kinetics and mechanism of reaction were investigated, and the results revealed that it follows a pseudo-first-order model for each pollutant.

Comparison of Disease Phenotype and Course among Elderly- and Early-Onset Inflammatory Bowel Diseases in the Middle East.

BACKGROUND: It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderly-onset inflammatory bowel disease (IBD). We aimed to seek differences in disease phenotype, course, complications, and treatment between early- and elderly-onset IBD patients. METHODS: This retrospective cohort study on registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) compared demographics, disease phenotype, disease activity, IBD-related surgery and medications between early- and elderly-onset IBD. A generalized linear regression model was used to investigate the relative risk of age at diagnosis adjusted for gender and disease duration for the outcomes. RESULTS: From 10048 IBD patients, 749 with early-onset (7.5%), and 472 (4.7%) elderly-onset IBD were enrolled: 855 (63.1%) ulcerative colitis (UC) and 366 (26.9%) Crohn's disease (CD). Left-sided colitis was more frequent among elderly-onset UC patients (P<0.001). Ileum and ileocolonic locations were the most common types in elderly-onset and early-onset CD patients, respectively. In comparison with elderly-onset UC, early-onset cases more often used prednisolone (22.1% vs. 11.4%, P=0.001), immunomodulators (44.9% vs 25.2%, P<0.001) and anti-tumor necrosis factors (TNF) (20.1% vs 11.9%, P=0.002). Elderly-onset UC patients had 0.7 times lower risk of aggressive phenotype (95%CI:0.6‒0.9, P=0.005). Early-onset CD was associated with higher use of prednisolone (27.7% vs 8.1%, P<0.001), immunomodulators (58.7% vs 41.8%, P=0.005) and anti-TNF (49.6% vs 35.4%, P=0.006). CONCLUSION: Early-onset IBD was associated with a more aggressive phenotype and higher prednisolone, immunomodulators, and anti-TNF use.

Association between frequency of processed and ultraprocessed food consumption with lifestyle habits score for cancer prevention among adults in Malaysia

@#Introduction: Cancer is the second leading cause of mortality globally. Processed and ultra-processed foods are reported to be high in energy, sugar, and unhealthy fats, while low in fibre, vitamins and minerals, that can increase the risk of cancer. Methods: A cross-sectional study involving adults aged 18-59 years was conducted in Peninsular Malaysia (n=122). Sociodemographic data were obtained through a questionnaire and lifestyle habits score for cancer prevention was assessed using MyGenomSihat©. The food frequency questionnaire used had four groups (i.e., unprocessed or minimally processed foods, processed culinary ingredients, processed foods, and ultra-processed foods) containing 53 food items to evaluate the frequency of food consumption. All data obtained were self-reported by the participants. Results: Mean age was 27.6±8.1 years with a majority (76.2%) having household income of less than <RM4,850. The results from MyGenomSihat© demonstrated that majority (53.3%) of subjects had average scores between 41-85, which is considered to be satisfactory lifestyle habits. Most Malaysian adults ate ultra-processed foods (32.9%) compared to processed foods (4.9%). However, there were no significant correlations between consumption of both processed and ultraprocessed food groups and lifestyle habits score for cancer prevention (r=-0.072, p=0.089 and r=-0.008, p=0.992, respectively). Conclusion: Most subjects had satisfactory lifestyle habits scores for cancer prevention. Interventions are needed to improve lifestyle habits among the targeted population for cancer prevention.

Effects of Dry Needling on Pain in Patients with Knee Osteoarthritis: A Preliminary Study.

Background: Osteoarthritis is one of the most common rheumatological diseases and is also considered as one of the causes of myofascial trigger points (MtrPs). Dry needling (DN) is one of the methods used for the treatment of the MtrPs. The aim of the current study was to investigate the effects of DN on pain in participants with knee osteoarthritis (KOA). Materials and Methods: In this before and after preliminary clinical trial study, patients with mild to moderate KOA were enrolled. In one session, after determining the location of trigger points in quadriceps and gastrocnemius muscles, the patients underwent DN. The pain was evaluated at baseline, by passing 4 days and 1 month from the intervention using the Visual Analog Scale (VAS). Results: Sixteen patients with a mean age of 56.5 (4.53) years old have completed the study and follow-up period. According to the ANOVA analysis, VAS values indicated a significant decrease in pain score at the 4th and 1 month after the intervention compared to baseline (P < 0.001). There was no significant difference between VAS at the 4th day of intervention and also 1 month later of intervention (P = 0.087). Conclusion: The application of one session DN can lead to improvement in pain intensity in participants with mild to moderate KOA.

Melatonin treatment improves cognitive deficits by altering inflammatory and neurotrophic factors in the hippocampus of obese mice.

Overweight and obesity are associated with an increased risk of developing dementia and cognitive deficits. Neuroinflammation is one of the most important mechanisms behind cognitive impairment in obese patients. In recent years, the neuroendocrine hormone melatonin has been suggested to have therapeutic effects for memory decline in several neuropsychiatric and neurological conditions. However, the effects of melatonin on cognitive function under obesity conditions still need to be clarified. The purpose of this study was to determine whether melatonin treatment can improve cognitive impairment in obese mice. To this end, male C57BL6 mice were treated with a high-fat diet (HFD) for 20 weeks to induce obesity. The animal received melatonin for 8 weeks. Cognitive functions were evaluated using the Y maze, object recognition test, and the Morris water maze. We measured inflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17A, and brain-derived neurotrophic factor (BDNF) in the hippocampus of obese mice. Our results show that HFD-induced obesity significantly impaired working, spatial and recognition memory by increasing IFN-γ and IL-17A and decreasing BDNF levels in the hippocampus of mice. On the other hand, melatonin treatment effectively improved all cognitive impairments and reduced TNF-α, IFN-γ, and IL-17A and elevated BDNF levels in the hippocampus of obese mice. Taken together, this study suggests that melatonin treatment could have a beneficial role in the treatment of cognitive impairment in obesity.

Somatic embryogenesis and ß-glucuronidase transformation in chickpea (Cicer arietinum cv. Bivanich).

BACKGROUND: Chickpea (Cicer arietinum L.) is an important kernel legume in the world. To optimize the plant tissue culture some experiments such as direct regeneration, proliferation, rooting shoots and somatic embryogenesis were done. METHODS AND RESULTS: In experiments were used direct regeneration and proliferation, various levels of plant growth regulators NAA (0 and 1.0 mg/l), BAP (0, 1, 3 and 5 mg/l) and three explants' types (epicotyl, cotyledon and embryonic axis). The results of both experiments showed that embryonic axis explant was better than other explants. The highest percentage was obtained in MS media containing 1 mg/l BAP and also 3 mg/l BAP and 0.1 mg/l NAA with an average of 72%. The highest average number of branches (4.66) was found in the proliferation of embryonic axis in MS medium containing 3 mg/l BAP. The highest rooting shoot (90%) was found in 1/2MS in B5 medium vitamins with 0.2 mg/l of IBA and 0.5 mg/l NAA. Somatic embryogenesis experiments were compared on the concentration gradient of 2,4-D in fine embryonic axis explants. The results displayed that the concentration gradient of 10 mg/l 2,4-D to 5 mg/l of 2,4-D and then to zero concentration showed the highest number of embryos. CONCLUSION: The best environment for regeneration embryos was MS medium with 2.5 mg/l of 2,4-D concentration gradient to zero. In this study, the PCR reaction showed the presence of the ß-glucuronidase (gus) marker gene in regenerated cotyledons for 20 min in all three strains studied.

Early life GABAA blockade alters the synaptic plasticity and cognitive functions in male and female rats.

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adults, has a critical contribution to balanced excitatory-inhibitory networks in the brain. Alteration in depolarizing action of GABA during early life is connected to a wide variety of neurodevelopmental disorders. Additionally, the effects of postnatal GABA blockade on neuronal synaptic plasticity are not known and therefore, we set out to determine whether postnatal exposure to bicuculline, a competitive antagonist of GABAA receptors, affects electrophysiologic changes in hippocampal CA1 neurons later on. To this end, male and female Wistar rats received vehicle or bicuculline (300 µg/kg) on postnatal days (PNDs) 7, 9 and 11, and then underwent different behavioral and electrophysiological examinations in adulthood. Postnatal exposure to bicuculline did not affect basic synaptic transmission but led to a pronounced decrease in paired-pulse facilitation (PPF) in CA1 pyramidal neurons. Bicuculline treatment also attenuated the long-term potentiation (LTP) and long-term depression (LTD) of CA1 neurons accompanied by decreased theta-burst responses in male and female adult rats. These electrophysiology findings together with the reduced brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex reliably explain the disturbance in spatial reference and working memories of bicuculline-treated animals. This study suggests that postnatal GABAA blockade deteriorates short- and long-term synaptic plasticity of hippocampal CA1 neurons and related encoding of spatial memory in adulthood.

Postnatal GABAA Receptor Activation Alters Synaptic Plasticity and Cognition in Adult Wistar Rats.

Early life alteration in the activity of gamma-aminobutyric acid (GABA) receptors is associated with long-lasting developmental effects on the brain and behavior. GABAA receptors act as excitatory rather than inhibitory in neonates. Excessive activation of GABAA receptors during the early postnatal period may affect cognitive functions later in life. In this study, we sought to determine whether neonatal activation of GABAA receptors with muscimol can alter the electrophysiology profile of hippocampal CA1 neurons and spatial learning and memory in adult rats. Male and female Wistar rat pups received a subcutaneous injection of either saline or muscimol (500 µg/kg) on postnatal days (PND) 7, 9, and 11 and then underwent different electrophysiology and behavioral experiments in adulthood. Early life treatment with muscimol did not alter the basic synaptic transmission but significantly reduced the paired-pulse facilitation (PPF) in the CA1 area. Neonatal application of muscimol led to a pronounced decrease in long-term potentiation (LTP) and long-term depression (LTD) in CA1 neurons along with a declined theta-burst responses in both sexes. We obtained some evidence that neonatal GABAA activation leads to reduced brain-derived neurotrophic factor (BDNF) in the hippocampus and prefrontal cortex. Our electrophysiology data was supported with spatial reference and working memory deficits in rats. This study provides the first detailed description of altered electrophysiology in hippocampal CA1 neurons in adult rats undergone GABAA activation early in life.

Mitigating spread of contamination in meat supply chain management using deep learning.

Industry 4.0 recommends a paradigm shift from traditional manufacturing to automated industrial practices, especially in different parts of supply chain management. Besides, the Sustainable Development Goal (SDG) 12 underscores the urgency of ensuring a sustainable supply chain with novel technologies including Artificial Intelligence to decrease food loss, which has the potential of mitigating food waste. These new technologies can increase productivity, especially in perishable products of the supply chain by reducing expenses, increasing the accuracy of operations, accelerating processes, and decreasing the carbon footprint of food. Artificial intelligence techniques such as deep learning can be utilized in various sections of meat supply chain management--where highly perishable products like spoiled meat need to be separated from wholesome ones to prevent cross-contamination with food-borne pathogens. Therefore, to automate this process and prevent meat spoilage and/or improve meat shelf life which is crucial to consumer meat preferences and sustainable consumption, a classification model was trained by the DCNN and PSO algorithms with 100% accuracy, which discerns wholesome meat from spoiled ones.

Persistent sexually dimorphic effects of adolescent THC exposure on hippocampal synaptic plasticity and episodic memory in rodents.

There is evidence that cannabis use during adolescence leads to memory and cognitive problems in young adulthood but little is known about effects of early life cannabis exposure on synaptic operations that are critical for encoding and organizing information. We report here that a 14-day course of daily Δ9-tetrahydrocannabinol treatments administered to adolescent rats and mice (aTHC) leads to profound but selective deficits in synaptic plasticity in two axonal systems in female, and to lesser extent male, hippocampus as assessed in adulthood. Adolescent-THC exposure did not alter basic synaptic transmission (input/output curves) and had only modest effects on frequency facilitation. Nevertheless, aTHC severely impaired the endocannabinoid-dependent long-term potentiation in the lateral perforant path in females of both species, and in male mice; this was reliably associated with impaired acquisition of a component of episodic memory that depends on lateral perforant path function. Potentiation in the Schaffer-commissural (S-C) projection to field CA1 was disrupted by aTHC treatment in females only and this was associated with both a deficit in estrogen effects on S-C synaptic responses and impairments to CA1-dependent spatial (object location) memory. In all the results demonstrate sexually dimorphic and projection system-specific effects of aTHC exposure that could underlie discrete effects of early life cannabinoid usage on adult cognitive function. Moreover they suggest that some of the enduring, sexually dimorphic effects of cannabis use reflect changes in synaptic estrogen action.

Neonatal NMDA blockade alters the LTP, LTD and cognitive functions in male and female Wistar rats.

There is compelling evidence that neonatal blockade of NMDA receptors by phencyclidine (PCP) is associated with cognitive impairment in adulthood but little is known about the effects of early life PCP treatment on synaptic function later in life. Here, we sought to determine whether early life exposure to PCP alters the electrophysiologic function of hippocampal CA1 neurons in adult rats. To this end, male and female Wistar rats received either saline or PCP (10 mg/kg) on postnatal days (PND) 7, 9, and 11, and then underwent separate behavioral and electrophysiology tests in adulthood. Neonatal PCP treatment did not alter basic synaptic transmission and had only a modest effect on frequency following (FF) capacity but significantly decreased the paired-pulse facilitation (PPF) in the Schaffer collateral (SC)-CA1 pathway. We found that PCP treatment significantly attenuated the long-term potentiation (LTP) and long-term depression (LTD) in CA1 neurons accompanied by pronounced alteration in complex response profile in adult rats. The electrophysiology data were comparable in male and female rats and reliably associated with impaired spatial reference and working memories in these animals. Overall, this study suggests that blockade of NMDA receptors during early life deteriorates the short-term and long-term synaptic plasticity and complex response profile of CA1 neurons in adulthood.

Long-term Efficacy of Combined Treatment in Patients with Idiopathic Achalasia.

BACKGROUND Several treatment strategies are available to treat achalasia. Although combined therapy has been used for several years, there are limited data on long-term outcomes. We aimed to determine its long-term efficacy in patients who were resistant or those with rapid relapse. METHODS In this prospective study, we reviewed the records of 1100 patients with achalasia, who were candidates for pneumatic balloon dilatation (PBD) in our center from 1996 to 2018. We enrolled 197 patients resistant to initial treatment or with rapid relapse of symptoms after three sessions of PBD. Clinical evaluation and time barium esophagogram (TBE) were done before treatment, a month afterward, and when clinical symptoms increased in order to confirm relapse, and at the end of follow-up. RESULTS A total of 168 patients accepted combined therapy. The mean duration of follow-up was 9.04 years. Achalasia symptom score (ASS) dropped from 10.82 to 3.62 a month after treatment and was 3.09 at the end of the follow-up (p = 0.0001 and 0.001). TBE had a decrease in mean height of barium one month after treatment (9.23 vs. 5.10, p = 0.001), and this reduction persisted until the end of follow-up (3.39, p = 0.001). Vantrappen score at the end of the follow-up showed 56 patients in excellent, 51 in good, 33 in moderate, and 14 in poor condition (89% acceptable response rate). CONCLUSION Our results showed the long-term efficacy of combined treatment in patients with achalasia who otherwise had to undergo a high-risk and costly procedure, which makes it a safe and effective alternative for myotomy.

Latest developments in nanofluid flow and heat transfer between parallel surfaces: A critical review.

The enhancement of heat transfer between parallel surfaces, including parallel plates, parallel disks, and two concentric pipes, is vital because of their wide applications ranging from lubrication systems to water purification processes. Various techniques can be utilized to enhance heat transfer in such systems. Adding nanoparticles to the conventional working fluids is an effective solution that could remarkably enhance the heat transfer rate. No published review article focuses on the recent advances in nanofluid flow between parallel surfaces; therefore, the present paper aims to review the latest experimental and numerical studies on the flow and heat transfer of nanofluids (mixtures of nanoparticles and conventional working fluids) in such configurations. For the performance analysis of thermal systems composed of parallel surfaces and operating with nanofluids, it is necessary to know the physical phenomena and parameters that influence the flow and heat transfer characteristics in these systems. Significant results obtained from this review indicate that, in most cases, the heat transfer rate between parallel surfaces is enhanced with an increase in the Rayleigh number, the Reynolds number, the magnetic number, and Brownian motion. On the other hand, an increase in thermophoresis parameter, as well as flow parameters, including the Eckert number, buoyancy ratio, Hartmann number, and Lewis number, leads to heat transfer rate reduction.

Perinatal fluoxetine dose-dependently affects prenatal stress-induced neurobehavioural abnormalities, HPA-axis functioning and underlying brain alterations in rat dams and their offspring.

Both untreated and SSRI antidepressant treated maternal depression during the perinatal period can pose both short-and long-term health risks to the offspring. Therefore, it is essential to have an effective SSRI treatment consisting of the lowest effective dose beneficial to the mother, without causing adverse effects on offspring development. The effects of prenatal stress on neurobehavioral outcomes were studied in the pregnant and lactating rat dam, and her offspring. Furthermore, stressed dams were treated with different doses of fluoxetine (FLX; 5, 10and 25 mg/kg) during pregnancy and the postpartum period. We found that prenatal stress-induced anxiety-and depressive-like behaviour and increased HPA-axis function in pregnant and postpartum dams, and in offspring. Maternal stress impaired object recognition but did not affect spatial memory in offspring. Prenatal stress decreased whole-brain serotonin and brain-derived-neurotrophic-factor, and increased interleukin-17 and malondialdehyde, but did not affect oxytocin and interleukin-6 in the brains of offspring. Maternal treatment with 5 mg/kg FLX during the perinatal period did not rescue any stress-induced anxiety/depressive-like behaviour in the pregnant and postpartum dam and had only a few rescuing effects in offspring. Maternal FLX treatment with 10 mg/kg did rescue most stress-induced anxiety-and depressive-like behaviour or HPA-axis-function in dams and offspring. The highest dose tested, 25 mg/kg FLX, had the rescuing properties in dams while having the same, or an even greater, detrimental effect as prenatal stress on offspring behaviour and molecular alterations in the brain. Our results show prenatal stress rescuing properties for FLX treatment in the pregnant and postpartum dam, with dose-dependent effects on the offspring.

The role of glutamate transporter-1 in firing activity of locus coeruleus neurons and nociception in rats.

Locus coeruleus (LC) is considered to be the main source of norepinephrine in the central nervous system (CNS) and plays important role in relieving pain in the body. Changes in the activity of synaptic excitatory amino acid transporters (EAATs) would be an applicable way to regulate synaptic transmission in the LC. In the present study, we examined the role of astrocytic glutamate transporter-1 (GLT1) in the firing activity of LC neurons and the sensation of pain in rats. Male Wistar rats were divided into three control (CNT), ceftriaxone (CFT) and dihydrokainic acid (DHK) groups. Animals were given intraperitoneal injections for nine consecutive days after which the electrophysiological and behavioral experiments were performed to determine the single-unit activity of LC neurons and pain sensation. Results of this study revealed that CFT as a well-known up-regulator of GLT1 expression decreases the latency of pain sensation in rats but inhibition of GLT1 activity by DHK showed no significant effects. Furthermore, the results obtained by single-unit recording from LC showed a significant decrease in evoked response in CFT group compared to the CNT group. Therefore, this study suggests that GLT1 might be considered as a potential therapeutic target for pain modulation in the future.

Alterations in the behavior, cognitive function, and BDNF level in adult male rats following neonatal blockade of GABA-A receptors.

Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the mature brain. At an early developmental period, it acts in an excitatory manner that influences many processes of proliferation, migration, and differentiation of the neurons. Previous evidence indicated that manipulation of the GABAergic system function by activation or blockade of its receptors during developmental periods leads to behavioral and cognitive abnormality in adulthood. Therefore, we examined the effects of neonatal blockade of GABA-A receptors by bicuculline on behavior, cognitive function, and hippocampal and prefrontal cortex (PFC) brain-derived neurotrophic factors level (BDNF) in adulthood. As a result, neonatal rats were treated with either bicuculline (75,150, and 300 µg/kg) or DMSO on postnatal days 7,9, and 11. These groups underwent the behavioral (open field, elevated plus maze, and hot plate) and learning and memory (passive avoidance learning and memory) tests in postnatal days (PNDs) 61-70. After the ending of the behavioral tests, the rats were sacrificed under deep anesthesia and the hippocampi and prefrontal cortex (PFC) of the brain were removed for assessing the BDNF mRNA expression. Our results indicated that neonatal administration of bicuculline at the highest dose increased passive avoidance memory and hippocampal BDNF level. Meanwhile, this drug at a low dose impaired this type of memory and increased PFC BDNF level. Besides, treatment with bicuculline during postnatal days increased anxiety and pain sensitivity in a dose-dependent manner. Taken together, these findings confirmed the notion that GABA-A receptors during the developmental period are important for programming neurobehavioral phenotypes in adult life.

Rapid Aging in the Perforant Path Projections to the Rodent Dentate Gyrus.

Why layers II/III of entorhinal cortex (EC) deteriorate in advance of other regions during the earliest stages of Alzheimer's disease is poorly understood. Failure of retrograde trophic support from synapses to cell bodies is a common cause of neuronal atrophy, and we accordingly tested for early-life deterioration in projections of rodent layer II EC neurons. Using electrophysiology and quantitative imaging, changes in EC terminals during young adulthood were evaluated in male rats and mice. Field excitatory postsynaptic potentials, input/output curves, and frequency following capacity by lateral perforant path (LPP) projections from lateral EC to dentate gyrus were unchanged from 3 to 8-10 months of age. In contrast, the unusual presynaptic form of long-term potentiation (LTP) expressed by the LPP was profoundly impaired by 8 months in rats and mice. This impairment was accompanied by a reduction in the spine to terminal endocannabinoid signaling needed for LPP-LTP induction and was offset by an agent that enhances signaling. There was a pronounced age-related increase in synaptophysin within LPP terminals, an effect suggestive of incipient pathology. Relatedly, presynaptic levels of TrkB-receptors mediating retrograde trophic signaling-were reduced in the LPP terminal field. LTP and TrkB content were also reduced in the medial perforant path of 8- to 10-month-old rats. As predicted, performance on an LPP-dependent episodic memory task declined by late adulthood. We propose that memory-related synaptic plasticity in EC projections is unusually sensitive to aging, which predisposes EC neurons to pathogenesis later in life.SIGNIFICANCE STATEMENT Neurons within human superficial entorhinal cortex are particularly vulnerable to effects of aging and Alzheimer's disease, although why this is the case is not understood. Here we report that perforant path projections from layer II entorhinal cortex to the dentate gyrus exhibit rapid aging in rodents, including reduced synaptic plasticity and abnormal protein content by 8-10 months of age. Moreover, there was a substantial decline in the performance of an episodic memory task that depends on entorhinal cortical projections at the same ages. Overall, the results suggest that the loss of plasticity and related trophic signaling predispose the entorhinal neurons to functional decline in relatively young adulthood.