Geon Ho Bahn

Alcohol and nicotine reduce cell proliferation and enhance apoptosis in dentate gyrus.

It is generally accepted that alcohol and nicotine affect learning ability and memory functions, especially in adolescents. In the present study, the effects of alcohol and nicotine on cell proliferation and apoptosis in the dentate gyrus of young rats were investigated. The results show that cell proliferation is suppressed by alcohol and nicotine. Furthermore, alcohol and nicotine increase the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells. Based on the results presented in this study, it can be suggested that alcohol- and nicotine-related impairment in learning and memory functions may be due to alcohol- and nicotine-induced suppression of new cell formation and acceleration of apoptosis, especially during adolescence.

A randomized controlled trial of the Korean version of the PEERS(®) parent-assisted social skills training program for teens with ASD.

Impaired social functioning is a hallmark feature of autism spectrum disorder (ASD), often requiring treatment throughout the life span. PEERS® (Program for the Education and Enrichment of Relational Skills) is a parent‐assisted social skills training for teens with ASD. Although PEERS® has an established evidence base in improving the social skills of adolescents and young adults with ASD in North America, the efficacy of this treatment has yet to be established in cross‐cultural validation trials. The objective of this study is to examine the feasibility and treatment efficacy of a Korean version of PEERS® for enhancing social skills through a randomized controlled trial (RCT).The English version of the PEERS® Treatment Manual (Laugeson & Frankel, 2010) was translated into Korean and reviewed by 21 child mental health professionals. Items identified as culturally sensitive were surveyed by 447 middle school students, and material was modified accordingly. Participants included 47 teens between 12 and 18 years of age with a diagnosis of ASD and a verbal intelligence quotient (IQ) ≥ 65. Eligible teens were randomly assigned to a treatment group (TG) or delayed treatment control group (CG). Primary outcome measures included questionnaires and direct observations quantifying social ability and problems directly related to ASD. Secondary outcome measures included scales for depressive symptoms, anxiety, and other behavioral problems. Rating scales for parental depressive symptoms and anxiety were examined to detect changes in parental psychosocial functioning throughout the PEERS® treatment. Independent samples t‐tests revealed no significant differences at baseline across the TG and CG conditions with regard to age (14.04 ± 1.64 and 13.54 ± 1.50 years), IQ (99.39 ± 18.09 & 100.67 ± 16.97), parental education, socioeconomic status, or ASD symptoms (p < 0.05), respectively. Results for treatment outcome suggest that the TG showed significant improvement in communication and social interaction domain scores on the Autism Diagnostic Observation Schedule, interpersonal relationship and play/leisure time on the subdomain scores of the Korean version of the Vineland Adaptive Behavior Scale (ps < 0.01), social skills knowledge total scores on the Test of Adolescent Social Skills Knowledge—Revised (p < 0.01), and decreased depressive symptoms on the Child Depression Inventory following treatment (p < 0.05). Analyses of parental outcome reveal a significant decrease in maternal state anxiety in the TG after controlling for potential confounding variables (p < 0.05). Despite cultural and linguistic differences, the PEERS® social skills intervention appears to be efficacious for teens with ASD in Korea with modest cultural adjustment. In an RCT, participants receiving the PEERS® treatment showed significant improvement in social skills knowledge, interpersonal skills, and play/leisure skills, as well as a decrease in depressive symptoms and ASD symptoms. This study represents one of only a few cross‐cultural validation trials of an established evidence‐based treatment for adolescents with ASD. Autism Res 2014, 7: 145–161.

Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients

The reduced incidence of cancer observed in schizophrenia patients may be related to differences in genetic background. It has been suggested that genetic predisposition towards schizophrenia is associated with reduced vulnerability to lung cancer, and p53 gene is one of the candidate genes. We tested the genetic association between schizophrenia and lung cancer by analyzing polymorphic sites in the p53 gene. Genotype and allele frequencies at two polymorphic sites in the p53 gene (BstUI and MspI restriction sites in exon 4 and intron 6, respectively) were studied in Korean schizophrenia (n=179) and lung cancer patients (n=104). Comparisons of the genotype and allele frequencies of the MspI polymorphism revealed significant differences between schizophrenia and lung cancer patients. The results suggest that the p53 polymorphism specifically found in schizophrenia patients may be associated with reduced vulnerability to lung cancer.

Subchronic Treatment of Donepezil Rescues Impaired Social, Hyperactive, and Stereotypic Behavior in Valproic Acid-Induced Animal Model of Autism

Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). We found that prenatal exposure of valproic acid (VPA) induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE) in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs) such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg) intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance.

The phosphodiesterase type-5 inhibitor, tadalafil, improves depressive symptoms, ameliorates memory impairment, as well as suppresses apoptosis and enhances cell proliferation in the hippocampus of maternal-separated rat pups

Early adverse experiences resulting from maternal separation may lead to neuronal cell death and eventually cause memory impairment. Maternal separation has been used to create a valid animal model of early life stress and a depression-like syndrome. The phosphodiesterase (PDE)-5 inhibitor, tadalafil (Cialis), is a widely prescribed agent for the treatment of erectile dysfunction. In this study, we investigated the effects of tadalafil on apoptosis and cell proliferation in the hippocampal dentate gyrus of rat pups following maternal separation. Specifically, the immobility time in the forced swim test was increased in the maternal-separated rat pups, and tadalafil treatment decreased the immobility time. The rat pups in the maternal separation group had deceased memory function compared to the rat pups in the maternal care group, and tadalafil treatment increased memory function of the rat pups in the maternal separation group. Apoptotic cell death in the hippocampal dentate gyrus was significantly increased in the maternal-separated rat pups, and tadalafil treatment suppressed maternal separation-induced apoptosis. In contrast, cell proliferation in the dentate gyrus was significantly decreased in the maternal-separated rat pups, and taldalafil treatment increased cell proliferation. The present results suggest that tadalafil improves depressive symptoms and alleviates memory impairment by suppressing apoptotic neuronal cell death and enhancing cell proliferation in maternal-separated rat pups.

Changes of empathy in medical college and medical school students: 1-year follow up study

BackgroundThis study aims to determine the correlation between medical education systems, medical college (MC) and medical school (MS), and empathy by investigating the changes in empathy among students with each additional year of medical education.MethodsThe subjects were MC and MS students who had participated in the same study the previous year. All participants completed the same self-report instruments: a questionnaire on sociodemographic characteristics, and the Korean edition of the Student Version of the Jefferson Scale of Empathy (JSE-S-K), Among 334 students, the final analysis was conducted on the data provided by 113 MC and 120 MS students, excluding 101 with incomplete data.ResultsThe age and sex did not affect the changes in empathy. Though the JSE-S-K score of MS was significantly higher than that of MC in initial investigation, this study found no difference of empathy between MC and MS.ConclusionEmpathy increased significantly after one year of medical education. The difference between two education systems, MC and MS, did not affect the changes in empathy.

PROTECTIVE EFFECT OF HYPERICUM PERFORATUM LINN (ST. JOHN'S WORT) AGAINST HYDROGEN PEROXIDE-INDUCED APOPTOSIS ON HUMAN NEUROBLASTOMA CELLS

The medicinal plant Hypericum perforatum Linn, commonly known as St. Johns wort, has been used as an antidepressant. To investigate whether St. Johns wort possesses a protective effect against hydrogen peroxide (H(2)O(2))-induced cytotoxicity in neuronal cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4,6-diamidino-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, flow cytometry analysis, DNA fragmentation assay, and caspase-3 enzyme assay were performed on SK-N-MC human neuroblastoma cells. Cells treated with H(2)O(2) exhibited several apoptotic features, while those pre-treated with St. Johns wort prior to H(2)O(2) exposure showed a decreased occurrence of apoptotic features. In addition, pre-treatment with St. Johns wort inhibited H(2)O(2)-induced increase in caspase-3 enzyme activity. These results suggest that St. Johns wort may exert a protective effect against H(2)O(2)-induced apoptosis in human neuroblastoma cells.

Nicotine administration decreases neuropeptide Y expression and increases leptin receptor expression in the hypothalamus of food-deprived rats

The effects of nicotine on the expressions of neuropeptide Y (NPY) and leptin receptor in the rat hypothalamus were investigated via immunohistochemistry. The results show that NPY expression is not affected in the arcuate nucleus (ARN) and is increased only slightly in the paraventricular nucleus (PVN) by nicotine administration under normal (i.e. fed) conditions and that leptin receptor expression is decreased slightly in the ARN and not affected in the PVN following nicotine treatment under the same conditions. Food deprivation enhanced NPY and suppressed leptin receptor expression in the ARN and PVN of the hypothalamus. Nicotine administration resulted in decreased NPY and increased leptin receptor levels.

The Relationship between Empathy and Medical Education System, Grades, and Personality in Medical College Students and Medical School Students

PURPOSE This study investigated the relationship between empathy and medical education system, grades, and personality in medical college (MC) students and medical school (MS) students. METHODS One hundred fifty-five MC students and 137 MS students participated in this study, completing questionnaires on sociodemographic data, Jefferson Scale of Empathy, S-version, Korean edition (JSE-S-K), and Temperament and Character Inventory (TCI). RESULTS Reward Dependence (RD), Cooperativeness (C), and Self-directedness+ Cooperativeness (SC), which are subscales of the TCI, correlated significantly with JSE-S-K score. Third-year students had significantly higher scores on the JSE-S-K than first-year students. MS students had significantly higher scores on the JSE-S-K and the SC subscale of the TCI than MC students. However, there were no significant differences in empathy with regard to age, sex, motivation toward medical science, club activity, and applied specialty. CONCLUSION These results suggest that empathy is associated with personality traits, such as RD, C, and SC, and medical education curriculum contributes incrementally to empathy for students. The difference in test scores for empathy between MC students and MS students might be due to differences in personality traits, such as SC.

The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy

Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD. The first generation (F1) VPA-exposed offspring exhibited autistic-like impaired sociability and increased marble burying. They also showed increased seizure susceptibility, hyperactivity and decreased anxiety. We mated the VPA-exposed F1 male offspring with naïve females to produce the second generation (F2), and then similarly mated the F2 to deliver the third generation (F3). Remarkably, the autism-like behavioural phenotypes found in F1 persisted to the F2 and F3. Additionally, the frontal cortices of F1 and F3 showed some imbalanced expressions of excitatory/inhibitory synaptic markers, suggesting a transgenerational epigenetic inheritance. These results open the idea that E/I imbalance and ASD-like behavioural changes induced by environmental insults in mice can be epigenetically transmitted, at least, to the third generation. This study could help explain the unprecedented increase in ASD prevalence.