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The precise manipulation of the neural stem cell (NSC)-derived neural differentiation is still challenging, and there is a technological barrier to regulate the axonal regeneration in a controlled manner. Here, we developed a microfluidic chip integrated with a microelectrode array as an axonal guidance platform. The microfluidic electrode array chip consisted of two compartments and a bridge microchannel that could isolate and guide the axons. We demonstrated that the NSCs were largely differentiated into neural cells as the electric field was applied to the microfluidic electrode array chip. We also confirmed the synergistic effects of the electrical stimulation (ES) and neurotrophic factor (NF) on axonal outgrowth. This microfluidic electrode array chip can serve as a central nervous system (CNS) model for axonal injury and regeneration. Therefore, it could be a potentially powerful tool for an

Photoplethysmography (PPG) is a noninvasive technique that can be used to conveniently measure heart rate (HR) and thus obtain relevant health‐related information. However, developing an automated PPG system is difficult, because its waveforms are susceptible to motion artifacts and between‐patient variation, making its interpretation difficult. We use deep neural network (DNN) filters to mimic the cognitive ability of a human expert who can distinguish the features of PPG altered by noise from various sources. Systolic (S), onset (O), and first derivative peaks (W) are recognized by three different DNN filters. In addition, the boundaries of uninformative regions caused by artifacts are identified by two different filters. The algorithm reliably derives the HR and presents recognition scores for the S, O, and W peaks and artifacts with only a 0.7‐s delay. In the evaluation using data from 11 patients obtained from PhysioNet, the algorithm yields 8643 (86.12%) reliable HR measurements from a total of 10 036 heartbeats, including some with uninformative data resulting from arrhythmias and artifacts.

Prenatal exposure to valproic acid (VPA) has been implicated in the manifestation of autism spectrum disorder (ASD)-like behavioral and functional changes both in human and rodents including mice and rats. The objective of this study was to determine metabolomics profiling and biomarkers related to VPA-induced symptoms resembling ASD using proton nuclear magnetic resonance (1H-NMR) spectral data. VPA was administered to pregnant rats at gestation day 12.5 and effects measured subsequently in male 4-week-old offspring pups. The sociability of VPA-treated animals was significantly diminished and exhibited ASD-like behavior as evidenced by reduction of social adaptation disorder and lack of social interactions. To find biomarkers related to ASD, the following were collected prefrontal brain cortices, urine bladder and blood samples directly from heart puncture. In all samples, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) displayed significant clustering pattern differences between control and treated groups. Valine, taurine, myo-inositol, 3-hydroxybutyrate and 1,3-dihydroxyacetone were significantly decreased in brain cortices in treated rats. Serum metabolites of glucose, creatine phosphate, lactate, glutamine and threonine were significantly increased in VPA-administered animals. Urinary metabolites of pimelate, 3-hydroxyisovalerate and valerate were significantly reduced in VPA-treated rat, whereas galactose and galactonate levels were elevated. Various metabolites were associated with mitochondrial dysfunction metabolism and central nervous system disorders. Data demonstrated that VPA-induced alterations in endogenous metabolites of serum, urine, and brain cortex which might prove useful as biomarkers for symptoms resembling ASD as a model of this disorder.

Although the use of IVIg has increased in various immune-driven diseases and even in pregnancy, the exact action mechanisms of IVIg are not fully understood. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) is a known receptor for α-2,6-sialylated IgG (sIVIg), which is responsible for the anti-inflammatory effect of IVIg. DC-SIGN is expressed on Hofbauer cells (HBCs) of the fetal villi of the placenta which act as an innate immune modulator at the maternal-fetal interface. Preeclampsia is a major complication in pregnancy and is related to IL-10, a cytokine with an important role in immune tolerance. DC-SIGN interaction with sIVIg in HBCs promoted IL-10 secretion through the activation of the caveolin-1/NF-κB pathway, especially in plasma lipid rafts. Consistent results were obtained for HBCs from patients with preeclampsia. Collectively, the stimulation of DC-SIGN

The rapidly acting antidepressants ketamine and scopolamine exert behavioral effects that can last from several days to more than a week in some patients. The molecular mechanisms underlying the maintenance of these antidepressant effects are unknown. Here we show that methyl-CpG-binding protein 2 (MeCP2) phosphorylation at Ser421 (pMeCP2) is essential for the sustained, but not the rapid, antidepressant effects of ketamine and scopolamine in mice. Our results reveal that pMeCP2 is downstream of BDNF, a critical factor in ketamine and scopolamine antidepressant action. In addition, we show that pMeCP2 is required for the long-term regulation of synaptic strength after ketamine or scopolamine administration. These results demonstrate that pMeCP2 and associated synaptic plasticity are essential determinants of sustained antidepressant effects.

Photoplethysmography (PPG) is often used in telemedicine because it enables convenient measurement and provides data related to cardiopulmonary function. However PPG is difficult analyze using an automated algorithm because of its vulnerability to motion artefacts and the diversity of the waveforms according to the characteristics of individuals and diseases. Recently, as the use of telemedicine has become more frequent due to the outbreak of COVID19, the application of deep neural network (DNN) technology in the analysis of PPG and selection of reliable data has increased. In this study, PPG was analyzed using DNN techniques to reproduce the long-term potential (LTP) phenomenon in the brain. Moreover, the reliability of measuring saturation pulse oxymetry (SPO2) simultaneously was evaluated using the LTP-DNN. The LTP-DNN was able to evaluate faultless data by inspecting 58 PPG datasets, including 29 fault data, and could determine the possibility of failure in SPO2 measurement as well. Even in a moving situation, the LTP-DNN provides more accurate heartrate (HR) measurements than commercial SPO2 devices do. It can also be used to normalize the PPG waveform to identify waveform differences between individuals.

Valproic acid is a clinically used mood stabilizer and antiepileptic drug. Valproic acid has been suggested as a teratogen associated with the manifestation of neurodevelopmental disorders, such as fetal valproate syndrome and autism spectrum disorders, when taken during specific time window of pregnancy. Previous studies proposed that prenatal exposure to valproic acid induces abnormal proliferation and differentiation of neural progenitor cells, presumably by inhibiting histone deacetylase and releasing the condensed chromatin structure. Here, we found valproic acid up-regulates the transcription of T-type calcium channels by inhibiting histone deacetylase in neural progenitor cells. The pharmacological blockade of T-type calcium channels prevented the increased proliferation of neural progenitor cells induced by valproic acid. Differentiated neural cells from neural progenitor cells treated with valproic acid displayed increased levels of calcium influx in response to potassium chloride-induced depolarization. These results suggest that prenatal exposure to valproic acid up-regulates T-type calcium channels, which may contribute to increased proliferation of neural progenitor cells by inducing an abnormal calcium response and underlie the pathogenesis of neurodevelopmental disorders.

Photoplethysmography (PPG) is easy to measure and provides important parameters related to heart rate and arrhythmia. However, automated PPG methods have not been developed because of their susceptibility to motion artifacts and differences in waveform characteristics among individuals. With increasing use of telemedicine, there is growing interest in application of deep neural network (DNN) technology for efficient analysis of vast amounts of PPG data. This study is about an algorithm for measuring a patient's PPG and comparing it with their own data stored previously and with the average data of several groups. Six deep neural networks were used to normalize the PPG waveform according to the heart rate by removing uninformative regions from the PPG, distinguishing between heartbeat and reflection pulses, dividing the heartbeat waveform into 10 segments and averaging the values according to each segments. PPG data were measured using telemedicine in both groups. Group 1 consisted of healthy people aged 25 to 35 years, and Group 2 consisted of patients between 60 and 75 years of age taking antihypertensive medications. The proposed algorithm could accurately determine which group the subject belonged with the newly measured PPG data (AUC = 0.998). On the other hand, errors were frequently observed in identification of individuals (AUC = 0.819).

Photoplethysmography (PPG) is easy to perform and provides a variety of measurements, including details of heart rate and arrhythmia. However, automated PPG methods have not been developed because of their susceptibility to motion artifacts and differences in waveform characteristics among individuals. With increasing use of telemedicine, there is growing interest in application of deep neural network (DNN) technology for efficient analysis of vast amounts of PPG data. This study proposes an automatic algorithm incorporating DNNs for individual and patient-group identification; this is achieved by selecting normally measured waveforms, deleting error regions, and normalizing the pulse wave to obtain 10 “section values” that can be easily compared to other waveforms. The proposed algorithm was able to distinguish between patients aged 60–75 years with diabetes and hypertension and healthy subjects aged 25–35 years (AUC = 0.998). On the other hand, errors were frequently observed in identification of individuals (AUC = 0.819).

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that produces rapid antidepressant action in some patients with treatment-resistant depression. However, recent data suggest that ∼50% of patients with treatment-resistant depression do not respond to ketamine. The factors that contribute to the nonresponsiveness to ketamine's antidepressant action remain unclear. Recent studies have reported a role for secreted glycoprotein Reelin in regulating pre- and postsynaptic function, which suggests that Reelin may be involved in ketamine's antidepressant action, although the premise has not been tested. Here, we investigated whether the disruption of Reelin-mediated synaptic signaling alters ketamine-triggered synaptic plasticity and behavioral effects. To this end, we used mouse models with genetic deletion of Reelin or apolipoprotein E receptor 2 (Apoer2), as well as pharmacological inhibition of their downstream effectors, Src family kinases (SFKs) or phosphoinositide 3-kinase. We found that disruption of Reelin, Apoer2, or SFKs blocks ketamine-driven behavioral changes and synaptic plasticity in the hippocampal CA1 region. Although ketamine administration did not affect tyrosine phosphorylation of DAB1, an adaptor protein linked to downstream signaling of Reelin, disruption of Apoer2 or SFKs impaired baseline NMDA receptor-mediated neurotransmission. These results suggest that maintenance of baseline NMDA receptor function by Reelin signaling may be a key permissive factor required for ketamine's antidepressant effects. Taken together, our results suggest that impairments in Reelin-Apoer2-SFK pathway components may in part underlie nonresponsiveness to ketamine's antidepressant action.

It is very important to rapidly detect the contamination of Enterococcus faecalis in fermented foods such as Korean Kimchi to maintain its freshness since Kimchi is exported to all over the world. However, gene sequence of E. faecalis is very similar among various Lactobacillus. So, there have been difficulties in its screening. We have designed primers based on Bile salt hydrolase gene of E. faecalis and applied them to PCR test. PCR band was identified only from E. faecalis and only from the mixture contaminated with E. faecalis. It means that the primers we designed are highly specific for distinguishing contamination of E. faecalis. It will be possible to precisely screen within 1 h, which will greatly contribute to the prevention of food poisoning and quick quarantine.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive/restricted behaviors. Although gene-environment interactions may explain the heterogeneous etiology of ASD, it is still largely unknown how the gene-environment interaction affects behavioral symptoms and pathophysiology in ASD. To address these questions, we used Cntnap2 knockout mice (genetic factor, G) exposed to valproic acid during embryonic development (environmental factor, E) as a gene-environment interaction (G × E) model. Paradoxically, the social deficits observed in the respective G and E models were improved in the G × E model; however, the high seizure susceptibility was more severe in the G × E -model than in the G and E models. Repetitive self-grooming and hyperactivity did not differ among the three models. The amplitudes of miniature excitatory postsynaptic currents in layer 2/3 pyramidal neurons of the medial prefrontal cortex were aberrant and similar in the G × E model when compared to the control group. Our findings suggest that the interaction of two risk factors does not always aggravate ASD symptoms but can also alleviate them, which may be key to understanding individual differences in behavioral phenotypes and symptom intensity.

T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and GSK3β-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.

It is very important to rapidly detect the contamination of Enterococcus faecalis in fermented foods such as Korean Kimchi to maintain its freshness since Kimchi is exported to all over the world. However, gene sequence of E. faecalis is very similar among various Lactobacillus. So, there have been difficulties in its screening. We have designed primers based on Bile salt hydrolase gene of E. faecalis and applied them to PCR test. PCR band was identified only from E. faecalis and only from the mixture contaminated with E. faecalis. It means that the primers we designed are highly specific for distinguishing contamination of E. faecalis. It will be possible to precisely screen within 1 h, which will greatly contribute to the prevention of food poisoning and quick quarantine.

The purpose of this study was to investigate the effect of a 12-week circuit training program on health-related physical fitness and metabolic syndrome risk factors in obese female college students. Twenty subjects with over 30% of accumulated body fat voluntarily participated and were randomly allocated to the control group (n=10) or circuit training group (n=10). The circuit training program consisted of 10 types of resistance and aerobic exercise and was performed 3 times per week for 12 weeks. Health-related physical fitness and metabolic syndrome risk factors were analyzed to elucidate the effect of the circuit training. Significant differences between groups were determined with two-way repeated analysis of variance and paired t-test. As a result of this study, body weight, % body fat, and body mass index in the circuit training group was significantly decreased compared to the control group. All health-related physical fitness indicators such as back strength, sit-up, sit-and-reach, and 1,600 m running time showed relative effects between groups or over time. Among the metabolic syndrome risk factors, waist measurement, triglyceride, and total cholesterol were significantly decreased but blood glucose, high-density lipo-protein cholesterol and low-density lipoprotein cholesterol did not show any significant difference. Therefore, the present data suggested that circuit training for 12 weeks may be effective in improving physical fitness and preventing metabolic diseases.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, featuring social communication deficit and repetitive/restricted behaviors as common symptoms. Its prevalence has continuously increased, but, till now, there are no therapeutic approaches to relieve the core symptoms, particularly social deficit. In previous studies, abnormal function of the glutamatergic neural system has been proposed as a critical mediator and therapeutic target of ASD-associated symptoms. Here, we investigated the possible roles of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in autism symptoms using two well-known autistic animal models, Cntnap2 knockout (KO) mice and in utero valproic acid-exposed ICR (VPA) mice. We found that Cntnap2 KO mice displayed decreased glutamate receptor expression and transmission. Contrarily, VPA mice exhibited increased glutamate receptor expression and transmission. Next, we investigated whether AMPAR modulators (positive-allosteric-modulator for Cntnap2 KO mice and antagonist for VPA mice) can improve autistic symptoms by normalizing the aberrant excitatory transmission in the respective animal models. Interestingly, the AMPAR modulation specifically ameliorated social deficits in both animal models. These results indicated that AMPAR-derived excitatory neural transmission changes can affect normal social behavior. To validate this, we injected an AMPAR agonist or antagonist in control ICR mice and, interestingly, these treatments impaired only the social behavior, without affecting the repetitive and hyperactive behaviors. Collectively, these results provide insight into the role of AMPARs in the underlying pathophysiological mechanisms of ASD, and demonstrate that modulation of AMPAR can be a potential target for the treatment of social behavior deficits associated with ASD.

SUMMARY Ketamine is a noncompetitive glutamatergic N-methyl-d-aspartate receptor (NMDAR) antagonist that exerts rapid antidepressant effects. Preclinical studies identify eukaryotic elongation factor 2 kinase (eEF2K) signaling as essential for the rapid antidepressant action of ketamine. Here, we combine genetic, electrophysiological, and pharmacological strategies to investigate the role of eEF2K in synaptic function and find that acute, but not chronic, inhibition of eEF2K activity induces rapid synaptic scaling in the hippocampus. Retinoic acid (RA) signaling also elicits a similar form of rapid synaptic scaling in the hippocampus, which we observe is independent of eEF2K functioni. The RA signaling pathway is not required for ketamine-mediated antidepressant action; however, direct activation of the retinoic acid receptor α (RARα) evokes rapid antidepressant action resembling ketamine. Our findings show that ketamine and RARα activation independently elicit a similar form of multiplicative synaptic scaling that is causal for rapid antidepressant action., Graphical Abstract, In brief Suzuki et al. examine the role of eEF2K and retinoic acid signaling pathways in synaptic plasticity and rapid antidepressant effects. Their study establishes a causal link between synaptic scaling and rapid antidepressant effects and proposes that this form of synaptic plasticity is a key synaptic substrate for rapid antidepressant action.

Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates. Along these differences are the male-specific increased expressions of postsynaptic proteins which are the NMDA and AMPA receptors in the prefrontal cortex. The vGluT1 presynaptic proteins, but not GAD, were upregulated in both sexes of TERT-tg mice, although it is more significantly pronounced in the male group. Here, we confirmed that the behavioral effect of TERT overexpression in mice was male-specific, suggesting that the aberration of this gene and its downstream pathways preferentially affect the functional development of the male brain, consistent with the male preponderance in ASD.

Background Depression is prevalent in patients with chronic kidney disease (CKD) and continues to increase in elderly adults. Therefore, the aim of our study was to examine the relationship between CKD and depression in older patients. Methods We conducted a cross-sectional study based on 2013 Korea National Health and Nutrition Examination Survey data. In total, data of 973 subjects aged ≥65 years were analyzed, and the estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Results The prevalence of depression in older adults was 4.1% in men and 8.8% in women (P=0.004). The prevalence of depression did not differ according to CKD stage in women (normal eGFR and CKD stages 1 and 2 women, 41/474 [8.6%]) vs. CKD stages 3-5 women, 6/63 [9.5%]); however, the prevalence of depression in men with CKD stages 3-5 (8/83 [9.6%]) was significantly higher than in men with normal eGFR and CKD stage 1 and 2 (10/353 [2.8%], P=0.010). Multivariate logistic regression analysis showed that the odds ratio for depression in men with CKD stages 3-5 was 3.822 (95% confidence interval, 1.229 to 11.879) after adjusting for social status and chronic diseases (P=0.021). Conclusion The prevalence of depression was higher in elderly women than in men, while the prevalence of depression increased in elderly men with CKD stages 3-5 and was almost equal to that of women. Therefore, elderly men with progressive renal function impairment should be counseled and monitored for psychological problems.

Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD.

Clinical findings show that a single subanesthetic dose of ketamine elicits rapid antidepressant effects. Accumulating data suggests that ketamine blocks the N-methyl-D-aspartate receptor and results in specific effects on intracellular signaling including increased brain-derived neurotrophic factor (BDNF) protein expression, which augments synaptic responses required for rapid antidepressant effects. To further investigate this potential mechanism for ketamine’s antidepressant action, we examined the effect of increasing ketamine doses on intracellular signaling, synaptic plasticity, and rapid antidepressant effects. Given that ketamine is often used at 2.5−10 mg/kg to examine antidepressant effects and 20−50 mg/kg to model schizophrenia, we compared effects at 5, 20 and 50 mg/kg. We found that intraperitoneal (i.p.) injection of low dose (5 mg/kg) ketamine produces rapid antidepressant effects, which were not observed at 20 or 50 mg/kg. At 5 mg/kg ketamine significantly increased the level of BDNF, a protein necessary for the rapid antidepressant effects, while 20 and 50 mg/kg ketamine did not alter BDNF levels in the hippocampus. Low concentration ketamine also evoked the highest synaptic potentiation in the hippocampal CA1, while higher concentrations significantly decreased the synaptic effects. Our results suggest low dose ketamine produces antidepressant effects and has independent behavioral and synaptic effects compared to higher doses of ketamine that are used to model schizophrenia. These findings strengthen our knowledge on specific signaling associated with ketamine’s rapid antidepressant effects.

For reported primer sets used to detect influenza A viruses (IAVs), we verified the nucleotide identities with 9,103 complete sequences of matrix (M) genes. At best, only 93.2% and 85.3% of the sequences had a 100% match with reported forward and reverse primers, respectively. Therefore, we designed new degenerate forward and reverse primers with 100% identity to 94.4% and 96.2% of compared genes, respectively, and the primer set was used with SYBR-based reverse-transcription real-time PCR (SYBR-RT-rtPCR) for lower detection limits. The sensitivity of SYBR-RT-rtPCR with the new primers was 10-fold higher than that with a conventional method in ~2.37% of all M genes in the database used in our study. We successfully increased the sensitivity of SYBR-RT-rtPCR by concentrating the viral ribonucleoprotein (RNP) using immunomagnetic beads and Triton X-100. The improved generic primer set and RNP concentration method may be useful for sensitive detection of IAVs.

Supplemental material, DS1_JVDI_10.1177_1040638719830760 for An optimized molecular method for detection of influenza A virus using improved generic primers and concentration of the viral genomic RNA and nucleoprotein complex by Ji-Woon Kim, Chung-Young Lee, Thanh Trung Nguyen, Il-Hwan Kim, Hyuk-Joon Kwon and Jae-Hong Kim in Journal of Veterinary Diagnostic Investigation

A visceral helminth of the squid, Todarodes pacificus, is reported from the East Sea, the Republic of Korea. Total 39 squid samples were purchased from a fish market in Jumunjin-eup, Gangneung-si (City) from August 2014 to July 2015 and were examined for helminth parasites with naked eyes and under a stereomicroscope after opening the abdominal cavity with a pair of scissors. Whitish larval worms were mainly found in the stomach and abdominal cavity of the squid. They were detected in 25 (64.1%) out of 39 squids examined, and the infection density was 7 larvae per infected squid. Spatula-shaped larvae were 8.2×2.0 mm in average size, round to slightly flattened anteriorly, with round hatching posteriorly, and had characteristic 4 tentacles with numerous hooklets in the scolex. The larvae were identified as the plerocercoid stage of Nybelinia surmenicola by their morphological features. This finding represents a new host record and the first report of N. surmenicola infection in T. pacificus squids from the east coast of Korea.

The valproic acid (VPA) animal model of autism spectrum disorder (ASD) is one of the most widely used animal model in the field. Like any other disease models, it can't model the totality of the features seen in autism. Then, is it valid to model autism? This model demonstrates many of the structural and behavioral features that can be observed in individuals with autism. These similarities enable the model to define relevant pathways of developmental dysregulation resulting from environmental manipulation. The uncovering of these complex pathways resulted to the growing pool of potential therapeutic candidates addressing the core symptoms of ASD. Here, we summarize the validity points of VPA that may or may not qualify it as a valid animal model of ASD.

Social support can relieve stress-induced behavioural outcomes, although its underlying molecular mechanisms are not fully understood. Here, we evaluated whether social interactions can prevent the restraint stress (RS)-induced cognitive impairments in male adolescent mice by utilizing molecular, cellular, and behavioural approaches. Acute RS in adolescent ICR mice impaired the working memory in the Y-maze test and memory consolidation and retrieval in the novel-object-recognition test (NORT). In addition, RS increased the extracellular signal-regulated kinases 1/2 phosphorylation (p-ERK1/2) in the prefrontal cortex (PFC) and corticosterone levels in the plasma. Interestingly, these outcomes were normalized by the presence of a conspecific animal (social support) during RS. RS also significantly upregulated the expression levels of known stress-relevant genes such as Egr1, Crh, and Crhr1, which were normalized by social support. Systemic injection of SL327 (an inhibitor of MEK1/2 that also blocks its downstream signal ERK1/2) prior to RS rescued the working memory impairments and the increased p-ERK1/2 while normalizing the expression of Egr1. Our results suggest that social support can alleviate the RS-induced cognitive impairments partly by modulating ERK1/2 phosphorylation and gene transcription in the PFC, and provide novel insights into the molecular mechanisms of the stress-buffering effects of social support.

Males are predominantly affected by autism spectrum disorders (ASD) with a prevalence ratio of 5:1. However, the underlying pathological mechanisms governing the male preponderance of ASD remain unclear. Recent studies suggested that epigenetic aberrations may cause synaptic dysfunctions, which might be related to the pathophysiology of ASD. In this study, we used rat offspring prenatally exposed to valproic acid (VPA) as an animal model of ASD. We found male-selective abnormalities in the kinetic profile of the excitatory glutamatergic synaptic protein expressions linked to N-methyl-D-aspartate receptor (NMDAR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and metabotropic glutamate receptor 5 (mGluR5) pathways in the prefrontal cortex of the VPA-exposed offspring at postnatal weeks 1, 2, and 4. Furthermore, VPA exposure showed a male-specific attenuation of the methyl-CpG-binding protein 2 (MeCP2) expressions both in the prefrontal cortex of offspring and in the gender-isolated neural progenitor cells (NPCs). In the gender-isolated NPCs culture, higher concentration of VPA induced an increased glutamatergic synaptic development along with decreased MeCP2 expression in both genders suggesting the role of MeCP2 in the modulation of synaptic development. In the small interfering RNA (siRNA) knock-down study, 50 pmol of Mecp2 siRNA inhibited the MeCP2 expression in male- but not in female-derived NPCs with concomitant induction of postsynaptic proteins such as PSD95. Taken together, we suggest that the male-inclined reduction of MeCP2 expression is involved in the abnormal development of glutamatergic synapse and male preponderance in the VPA animal models of ASD.

A substantial proportion of patients with autism spectrum disorder (ASD) display hyperactivity as a comorbid symptom. Exposure to valproic acid (VPA) during pregnancy produces ASD-like core behavioral phenotypes as well as hyperactivity in offspring both in human and experimental animals, which makes it a plausible model to study ASD-related neurobiological processes. In this study, we examined the effects of two of currently available attention defecit hyperactivity disorder (ADHD) medications, methylphenidate (MPH) and atomoxetine (ATX) targeting dopamine and norepinephrine transporters (DAT and NET), respectively, on hyperactive behavior of prenatally VPA-exposed rat offspring. In the prefrontal cortex of VPA exposed rat offspring, both mRNA and protein expression of DAT was increased as compared with control. VPA function as a histone deacetylase inhibitor (HDACi) and chromatin immunoprecipitation experiments demonstrated that the acetylation of histone bound to DAT gene promoter was increased in VPA-exposed rat offspring suggesting epigenetic mechanism of DAT regulation. Similarly, the expression of NET was increased, possibly via increased histone acetylation in prefrontal cortex of VPA-exposed rat offspring. When we treated the VPA-exposed rat offspring with ATX, a NET selective inhibitor, hyperactivity was reversed to control level. In contrast, MPH that inhibits both DAT and NET, did not produce inhibitory effects against hyperactivity. The results suggest that NET abnormalities may underlie the hyperactive phenotype in VPA animal model of ASD. Profiling the pharmacological responsiveness as well as investigating underlying mechanism in multiple models of ASD and ADHD may provide more insights into the neurobiological correlates regulating the behavioral abnormalities.

Cytoplasmic polyadenylation binding protein 1 (CPEB1) is a RNA binding protein, which regulates translation of target mRNAs by regulating polyadenylation status. CPEB1 plays important roles in the regulation of germline cell development by modulating cell cycle progression through the polyadenylation of target mRNAs such as cyclin B1. Similar mechanism is reported in proliferating astrocytes by us, although CPEB1 is involved in the transport of target mRNAs as well as local translation at dendritic spines. In this study, we found the expression of CPEB1 in cultured rat primary neural progenitor cells (NPCs). EGF stimulation of cultured NPCs induced rapid phosphorylation of CPEB1, a hallmark of CPEB1-dependent translational control along with cyclin B1 polyadenylation and translation. EGF-induced activation of ERK1/2 and Aurora A kinase was responsible for CPEB1 phosphorylation. Pharmacological inhibition studies suggested that ERK1/2 is involved in the activation of Aurora A kinase and regulation of CPEB1 phosphorylation in cultured NPCs. Long-term incubation in EGF resulted in the down-regulation of CPEB1 expression, which further increased expression of cyclin B1 and cell cycle progression. When we down-regulated the expression of CPEB1 in NPCs by siRNA transfection, the proliferation of NPCs was increased. Increased NPCs proliferation by down-regulation of CPEB1 resulted in eventual up-regulation of neuronal differentiation with increase in both pre- and post-synaptic proteins. The results from the present study may suggest the importance of translational control in the regulation of neuronal development, an emerging concept in many neurodevelopmental and psychiatric disorders such as autism spectrum disorder.