Fluoxetine Up-Regulates Bcl-xL Expression in Rat C6 Glioma Cells

OBJECTIVE: To analyze both differentially expressed genes and the Bcl-xL protein expression after acute and chronic treatment with fluoxetine in rat C6 glioma cells. METHODS: C6 glioma cells were cultured for 24 h or 72 h after treatment with 10 microM fluoxetine, and gene expression patterns were observed using microarray and qRT-PCR. Then, cells were cultured for 6 h, 24 h, 72 h or 96 h after treatment with 10 microM fluoxetine, and the expression of Bcl-xL protein was measured using western blot. RESULTS: As determined by microarray, treatment with fluoxetine for 24 h up-regulated 33 genes (including Bcl-xL and NCAM140) and down-regulated 7 genes (including cyclin G-associated kinase). Treatment with fluoxetine for 72 h up-regulated 53 genes (including Gsalpha and Bcl-xL) and down-regulated 77 genes (including Galphai2 and annexin V). Based on the qRT-PCR results, there was an increase in Gsalpha mRNA and a decrease in Galphai2 mRNA at 72 h in fluoxetine-treated cells as compared to control, a result that was consistent with microarray. We also observed an increase in Bcl-xL mRNA (both at 24 h and at 72 h) in fluoxetine-treated cells as compared to control, demonstrating a tendency to increase gradually. Bcl-xL protein expression increased as the duration of fluoxetine treatment increased. CONCLUSION: These results suggest that chronic treatment with fluoxetine not only initiates the cAMP pathway through inducing Gsalpha expression but also induces Bcl-xL expression, thus inhibiting apoptosis.

The Effects of Venlafaxine and Dexamethasone on the Expression of HSP70 in Rat C6 Glioma Cells

OBJECTIVE: The present study aimed to determine the intracellular action of the antidepressant, venlafaxine, in C6 glioma cells using heat shock protein 70 (HSP70) immunocytochemistry and HSP70 Western blots; HSP70 is known to be associated with stress and depression. METHODS: The extent of HSP70 expression was measured after rat C6 glioma cells were treated with 1) dexamethasone only, 2) venlafaxine only, 3) simultaneous venlafaxine and dexamethasone, or 4) dexamethasone after venlafaxine pretreatment. Dexamethasone (10 microM, 6 hours) did not affect the level of HSP70 expression relative to control. RESULTS: Short-term (1 hour) venlafaxine treatment significantly increased the level of HSP 70 expression. Simultaneous long-term (72 hours) venlafaxine and dexamethasone treatment significantly reduced the level of HSP70 expression. Dexamethasone treatment administered following long-term (24 and 72 hours) pretreatment with venlafaxine also significantly reduced the level of HSP70 expression. CONCLUSION: Short-term treatment with venlafaxine increases the expression of HSP70, but prolonged treatment with dexamethasone suppresses the venlafaxine-induced expression of HSP70. These findings suggest that HSP70 and dexamethasone play a significant role in the pathophysiology of depression.

Chronic Treatment of Fluoxetine Increases Expression of NCAM140 in the Rat Hippocampus

OBJECTIVES: Most of the mechanisms reported for antidepressant drugs are the enhancement of neurite outgrowth and neuronal survival in the rat hippocampus. Neural cell adhesion molecule 140(NCAM140) has been implicated as having a role in cell-cell adhesion, neurite outgrowth, and synaptic plasticity. In this report, we have performed to elucidate a correlation among chronic antidepressant treatments, NCAM140 expression, and activation of phosphorylated cyclicAMP responsive element binding protein(pCREB) which is a downstream molecule of NCAM140-mediated intracellular signaling pathway in the rat hippocampus. METHODS: Fluoxetine(10mg/kg) was injected acutely(daily injection for 5days) or chronically(daily injection for 14days) in adult rats. RNA and protein were extracted from the rat hippocampus, respectively. Real-time RTPCR was performed to analyze the expression pattern of NCAM140 gene and western blot analyses for the activation of the phosphorylation ratio of CREB. RESULTS: Chronic fluoxetine treatments increased NCAM140 expression 1.3 times higher than control in rat hippocampus. pCREB immunoreactivity in the rat hippocampus with chronic fluoxetine treatment was increased 4.0 times higher than that of control. CONCLUSION: Chronic fluoxetine treatment increased NCAM140 expression and pCREB activity in the rat hippo-campus. Our data suggest that NCAM140 and pCREB may play a role in the clinical efficacy of antidepressants promoting the neurite outgrowth and neuronal survival.

Increased Transforming Growth Factor-beta1 in Alcohol Dependence

Ethanol and its metabolite acetaldehyde increase transforming growth factor beta1 (TGF-beta1) expression in animal studies. TGF-beta1 is related with the hepatic stellate cell (the key element of hepatic fibrogenesis) and the radial glia (the key element of neuronal migration). Blood samples were collected from 41 patients with alcohol dependence, TGF-beta1 levels measured by ELISA were compared with 41 normal subjects. Plasma TGF-beta1 levels in the patients with alcohol dependence (1,653.11+/-532.45 pg/mL) were significantly higher than those of healthy subjects (669.87+/-366.53 pg/mL) (P=0.000). Patients with or without liver pathology showed no difference in TGF-beta1 (P=0.36). Increased TGF-beta1 may mediate deleterious effect of alcohol such as hepatic fibrosis and suppressed neuronal developments in alcohol dependence patients.

Epigenetics and Psychiatric Disorders

In the post-genomic era, the mechanisms controlling activation of genes are thought to be more important. Gene-environment interactions are crucial in both development and treatment of psychiatric disorders as they are complex genetic disorders. Epigenetics is defined as a change of gene expression that occurs without a change of DNA sequence and can be heritable by certain mechanisms. Epigenetic changes play essential roles in control of gene activation. DNA methylation, chromatin remodeling and RNAi act as key mechanisms for epigenetic modifications of genes. Here, we review the basic mechanisms of epigenetics and discuss their potential involvement of human diseases, including psychiatric disorders.

Heat Shock Proteins as Molecular Chaperons in Neuropsychiatry

Recent researches have shown that important cellular-based autoprotective mechanisms are mediated by heat-shock proteins(HSPs), also called 'molecular chaperones'. HSPs as molecular chaperones are the primary cellular defense mechanism against damage to the proteome, initiating refolding of denatured proteins and regulating degradation after severe protein damage. HSPs also modulate multiple events within apoptotic pathways to help sustain cell survival following damaging stimuli. HSPs are induced by almost every type of stresses including physical and psychological stresses. Our nervous system in the brain are more vulnerable to stress and damage than any other tissues due to HSPs insufficiency. The normal function of HSPs is a key factor for endogenous stress adaptation of neural tissues. HSPs play an important role in the process of neurodevelopment, neurodegeneration, and neuroendocrine regulation. The altered function of HSPs would be associated with the development of several neuropsychiatric disorders. Therefore, an understanding of HSPs activities could help to improve autoprotective mechanism of our neural system. This paper will review the literature related to the significance of HSPs in neuropsychiatric field.

EEG A1, A2, and Percent Asymmetry Indices in Major Depressive Disorder; The Importance of Symptom Severity of Depression and Anxiety / 신경정신의학

OBJECTIVES: In this study we investigated characteristics of asymmetry pattern of EEG in patients with major depressive disorder according to the severity of depression and anxiety symptoms, employing A1, A2, and Percent (PCT) asymmetry indices. METHODS: Subjects involved in this study were 11 healthy controls and 11 patients with major depressive disorder who have taken no medicines for four weeks just before the study. These subjects were selected so that the two groups can have no difference in gender and age. Beck Depression Inventory (BDI), 17-item Hamilton Depression Rating Scale (HDRS), Zung's Self-Rating Depression Scale (SDS) and Spielberger's State-Trait Anxiety Inventory (STAI) were used to evaluate depression and anxiety symptoms, respectively. Resting EEG was recorded from F3, F4, C3, C4, T7, T8, O1 and O2 electrode sites. RESULTS: The temporal region showed a difference in A1, A2, and PCT asymmetry indices between the depression group and the control group. Frontal (F3, F4) and temporal (T7, T8) regions showed correlation between STAI-T score and A1, A2, and PCT asymmetry indices. CONCLUSION: The results of this study showed that EEG A1, A2, and PCT asymmetry indices can be used as useful indices for depression. Also, it was found that trait anxiety had influence on A1, A2, and PCT asymmetry indices.

No Associations between Schizophrenia and D22S280 Marker on Synapsin III Gene in Korean Males

OBJECTIVES: Synapsin III near VCFS region on chromosome 22q affects. It could be an interesting candidate gene for schizophrenia. D22S280 is a highly polymorphic genetic marker residing in synapsin III. We examined association of D22S280 marker on synapsin III with Korean patients with schizophrenia. METHODS: The subjects were 46 male Korean patients with schizophrenia and 60 male normal controls. Using polymerase chain reaction, gel electrophoresis, ABI 310 genetic analyzer, and GeneScan Collection 3.1 software, we confirmed genotypes of D22S280 marker. We examined Hardy-Weinberg equilibrium and case-control association using SAS/Genetic 9.1.3. RESULTS: Genotypes of both schizophrenia and control groups were in Hardy-Weinberg equilibrium. We could not find any significant statistical differences in allele-wise(chi-square=10.4, df=6, p=0.098) and genotype-wise (chi-square=22.1 df=19, p=0.258) analyses of D22S280 marker between schizophrenia and normal controls. Individual allele analyses with df=1 showed significant differences in A1(p=0.025) and A7(p=0.034) allele, which were not significant following Bonferroni corrections(A1 : p=0.177, A7 : p=0.235). CONCLUSION: We couldn't find any association between schizophrenia and the synapsin III gene. Given the small number of subjects studied, further investigations are needed.

The Feasibility Test of Korean Medication Algorithm for the Treatment with Schizophrenic Patients(I): Analysis Focusing on the Effectiveness of Treatment / 대한정신약물학회지

OBJECTIVES: The Korean College of Neuropsychopharmacology and the Korean Academy of Schizophrenia developed the Korean algorithm project for schizophrenia to aid clinical decisions. The purpose of this study was to assess the feasibility of Korean Medication Algorithm for Schizophrenia patients in clinical settings in Korea. METHODS: A total of 108 schizophrenia and schizophreniform disorder patients were enrolled at 19 centers and treated according to the algorithm. PANSS (Positive and Negative Symptom Scale) and CGI (Clinical Global Impression) were used to evaluate symptom severity. Also UKU (UKU side effect rating scale) and LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale), DAI-10 (Drug Attitude Inventory-10), PPS (Patient Preference Scale), SWN (Subjective Well-Being under Neuroleptic treatment) and WHOQOL (World Health Organization Quality of Life) were used to evaluate tolerability and satisfaction of patient respectively. RESULTS: Overall ratings including symptom severity, compliance of medication, side effect of medication, quality of life were favorable. The treatment response (PANSS improvement > or = 20%) rate was 63%, 75% at the first Clinical decision point (CDP) and 4 month respectively. CONCLUSION: Symptom improvement, tolerability and quality of life were all favorable. These results suggest that this algorithm can be useful in clinical practices.

Naltrexone influences protein kinase C epsilon and integrin alpha7 activity in SH-SY5Y neuroblastoma cells

Alcohol influences the neuroadaptation of brain cells where receptors and enzymes like protein kinase C (PKC) exist. Naltrexone acts on opioid receptors. However, other mechanisms of action remain unknown. We prepared SH-SY5Y neuroblastoma cells, and fed them with 150 mM ethanol for 72 h followed by treatment with naltrexone for 24 h. We performed microarray analysis and reverse transcriptase-polymerase chain reaction. Our results showed that PKC epsilon increased 1.90 times and showed an overall decreasing pattern as time increased. Phosphorylated ERK also increased 2.0 times according to the change of PKC epsilon. Integrin alpha7 increased 2.32 times and showed an increasing pattern as time increased. In conclusion, naltrexone influences PKC epsilon neuronal signaling system and endothelial adhesion molecule integrin alpha7 in addition to the well-known opioid system.

Gene Expression Profiling of SH-SY5Y Human Neuroblastoma Cells Treated with Ginsenoside Rg1 and Rb1

OBJECTIVES: The ginsenoside Rg1 and Rb1, the major components of ginseng saponin, have neurotrophic and neuroprotective effects including promotion of neuronal survival and proliferation, facilitation of learning and memory, and protection from ischemic injury and apoptosis. In this study, to investigate the molecular basis of the effects of ginsenoside on neuron, we analyzed gene expression profiling of SH-SY5Y human neuroblastoma cells treated with ginsenoside Rg1 or Rb1. METHODS: SH-SY5Y cells were cultured and treated in triplicate with ginsenoside Rg1 or Rb1(80micrometer, 40micrometer, 20micrometer). The proliferation rates of SH-SY5Y cells were determined by MTT assay and microscopic examination. We used a high density cDNA microarray chip that contained 8K human genes to analyze the gene expression profiles in SH-SY5Y cells. We analyzed using the Significance Analysis of Microarray(SAM) method for identifying genes on a microarray with statistically significant changes in expression. RESULTS: Treatment of SH-SY5Y cells with 80microliter ginsenoside Rg1 or Rb1 for 36h showed maximal proliferation compared with other concentrations or control. The results of the microarray experiment yielded 96 genes were upregulated(> or =3 fold) in Rg1 treated cells and 40 genes were up-regulated(> or =2 fold) in Rb1 treated cells. Treatment with ginsenoside Rg1 for 36h induced the expression of some genes associated with protein biosynthesis, regulation of transcription or translation, cell proliferation and growth, neurogenesis and differentiation, regulation of cell cycle, energy transport and others. Genes associated with neurogenesis and neuronal differentiation such as SCG10 and MLP increased in ginsenoside Rg1 treated cells, but such changes did not occur in Rb1- group. CONCLUSION: Our data provide novel insights into the gene mechanisms involved in possible role for ginsenoside Rg1 or Rb1 in mediating neuronal proliferation or cell viability, which can elicit distinct patterns of gene expression in neuronal cell line. Ginsenoside Rg1 have more broad and strong effects than ginsenoside Rb1 in gene expression and related cellular physiology. In addition, we suggest that SCG10 gene, which is known to be expressed in neuronal differentiation during development and neuronal regeneration during adulthood, may have a role in enhancement of activity dependent synaptic plasticity or cytoskeletal regulation following treatment of ginsenoside Rg1. Further, ginsenoside Rg1 may have a possible role in regeneration of injured neuron, promotion of memory, and prevention from aging or neuronal degeneration.

Effects of Venlafaxine and Dexamethasone Treatment on HSP70 Expression in Rat C6 Glioma Cells

OBJECT: The intracellular action of the antidepressant, venlafaxine, was studied in C6-gliomas using heat shock protein 70(HSP70) immunocytochemistry and HSP70 Western blots because HSP70 is associated with stress and depression. METHODS: To examine how the glucocorticoid affects the expression of HSP70 in nerve cells, the rat C6 glioma cell was treated with dexamethasone for 6 hours. In addition, venlafaxine was administered to the experimental groups of C6 glioma cells for 1, 6, 24, and 72 hours each, after which the expression of HSP70 was investigated. Finally, venlafaxine and dexamethasone were simultaneously administered to the experimental groups for 1, 6, 24, and 72 hours, followed by an investigation of the expression of HSP70. RESULTS: The short term(1 hour) venlafaxine treatment significantly increased the level of HSP70 expression. The short term treatment of venlafaxine with dexamethasone also increased the level of HSP70 expression but this reduction was not statistically significant. The long term(72 hours) venlafaxine with dexamethasone treatment significantly reduced the level of HSP70 expression. The long term treatment of venlafaxine also reduced the level of HSP70 expression but this reduction was not statistically significant. Dexamethasone(10uM, 6hours) did not affect the level of HSP70 expression compared with controls. CONCLUSION: Venlafaxine increases the expression of HSP70 at short term treatment, but prolonged treatment with dexamethasone suppresses the expression of HSP70.

Acute Alcohol Responses and Personality Traits by Aldehyde Dehydrogenase 2 Genotype Variances in Patients with Alcohol Dependence

OBJECTIVES: The purpose of this study is to evaluate the pathophysiology of alcoholics by investigating the differences in frequency of Aldehyde Dehydrogenase 2(ALDH2) genotypes and ALDH2 alleles between patients with alcohol dependence and controls, and the differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances. METHODS: The authors selected 98 patients with alcohol dependence and 53 controls. Self-report questionnaires for acute reponses after alcohol ingestion, the AUI(Alcohol Use Inventory), and the NEO-PI-R(NEO Personality Inventory Revised) were given to all patients with alcohol dependence. ALDH2 genotypes were typed with Mbo II RFLP(Restriction Fragment Length Polymorphism) method in 53 controls and 98 patients with alcohol dependence. The authors divided alcoholic patients into two groups according to the presence of variant ALDH22 allele; normal ALDH2 alcoholics(N=87) and variant ALDH2 alcoholics(N=11). RESULTS: 1) The genotypic frequencies of subjects with ALDH21/1 were higher and those with ALDH21/2 and ALDH22/2 were lower in patients than in controls. 2) Alcohol dependence could be found in ALDH22/2 homozygote individuals. 3) Variant ALDH2 alcoholics had more family problems in the AUI than normal ALDH2 alcoholics. 4) Variant ALDH2 alcoholics experienced more flushing and cardiovascular responses after alcohol ingestion than normal ALDH2 alcoholics. 5) Variant ALDH2 alcoholics had less altruistic personality traits in the NEO-PI-R than normal ALDH2 alcoholics. 6) Variant ALDH2 alcoholics tended to have more tolerance to alcohol than normal ALDH2 alcoholics. CONCLUSION: Variant ALDH22 allele might play a protective role in the pathogenesis of alcohol dependence and there were several significant differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances.

The Influences of Risperidone and Clozapine on Body Weight and Glucose Level in Patients with Chronic Schizophrenia: Comparison Study with Haloperidol

OBJECT: The goal of this study was to examine the changes in body weight and glucose levels of the patients treated with risperidone, clozapine or haloperidol in order to compare the effect of risperidone or clozapine with that of haloperidol. METHODS: For nine months(January to September, 2003), a prospective study was performed in 60 patients with chronic schizophrenia who were in Seoul National Hospital. Two-week period was required for a drug wash-out. The patients were randomly assigned to risperidone, clozapine and haloperidol groups. They were given risperidone(n=20), clozapine(n=20) and haloperidol(n=20), respectively, everyday for 12 weeks. To examine the effects of these drugs on body weight and fasting glucose levels, we measured body weight and glucose levels of all the patients first without the drug treatment and at each end of 4, 8, and 12-week periods with the treatment. And we examined the differences among three groups in the changes of body weight and fasting glucose levels. RESULTS: There were no significant differences in the changes of the body weight and fasting glucose levels between the atypical antipsychotics(risperidone or clozapine) and the typical antipsychotics(haloperidol). CONCLUSION: The study in the patients with chronic schizophrenia suggests that risperidone or clozapine do not cause any additional effects on body weight or glucose levels compared to haloperidol.

Fluoxetine-induced Changes on Activity of Tryptophan Hydroxylase at RBL-2H3 Cells / 대한정신약물학회지

OBJECTIVES: The aim of the present study is to explore the effect of fluoxetine on transcription, translation and activity of tryptophan hydroxylase (TPH), and intracellular level of serotonin. METHODS: The expression level of the TPH mRNA and the protein, the TPH enzyme activity, and the intracellular level of serotonin were explored at the fluoxetine-treated RBL-2H3 cells. Real-time RT-PCR and immunoblotting analysis confirmed changes in the expression of TPH mRNA and protein. The activity of TPH was measured using [3H]tryptophan. The intracellular level of serotonin was measured by HPLC. RESULTS: The TPH activity was gradually increased on time from 24hr to 72hr. The real-time RT-PCR also revealed that the TPH mRNA was increased at 12, 24 and 72hr in the fluoxetine-treated RBL-2H3 cells. The immunoblotting analysis also revealed that the TPH protein was decreased at 72hr in the fluoxetine-treated RBL-2H3 cells. The intracellular level of serotonin was increased at 48hr after treatment of fluoxetine. CONCLUSION: Fluoxetine induced the increases of the TPH mRNA, the TPH enzyme activity and intracellular level of serotonin, and the decrease of the TPH protein expression at the RBL- 2H3 cells.

Characterization of Differentially Expressed Genes upon Chronic Fluoxetine Treatment in Rat C6 Glioma Cells / 대한정신약물학회지

OBJECTIVE: The aim of this study was to identify diffrentially regulated genes after the treatment of fluoxetine in rat C6 glioma cells using cDNA microarray chip techniques and real-time RT-PCR. METHODS: Cells were incubated for 24 hours, and for 72 hours with or without 10 uM fluoxetine. Total RNAs extracted from cells were reversely transcribed to cDNA. These cDNA were used to carry out cDNA microarray chip. A part of the up-/down-regulated genes in cDNA microarray result were confirmed by real-time RT-PCR. RESULTS: 1) Genes in fluoxetinetreated cells for 72 hours (chronic treatment) were more regulated than that in fluoxetine-treated cells for 24 hours (acute treatment). 2) The expression level of Gs gene in fluoxetine-treated cells for 24 hours hardly altered, but that of Gs in fluoxetine-treated cells for 72 hours significantly increased. The expression of Gi2 also decreased in 72 hours in relation to 24 hours after the administration of fluoxetine. 3) The expression level of NCAM140 gene in fluoxetine-treated cells was higher than that in control cells. CONCLUSION: We identified genes (Gs, Gi2 and NCAM140) related to neural plasticity and intracellular signal transduction cascade from our result. This implies that fluoxetine may inhibit atrophy or death of impaired neural cells by promoting neurite outgrowth.

Fluoxetine Pretreatment Exert Time-Dependent Inhibits the Dexamethasone-Mediated Heat Shock Protein 70 Expression in Rat C6 Glioma Cells / 대한정신약물학회지

OBJECTIVE: The aim of this study was to examine the effect of dexamethasone and fluoxetine on the expression of 70 kDa heat shock protein (HSP70) in C6 glioma cells. METHODS: The C6 glioma cells belong to control group were incubated with DMEM culture solution, the cells belong to dexamethasone group were incubated with dexamethasone for 6 hours, and the cells belong to fluoxetine group were incubated with fluoxetine for 1, 6, 24, and 72 hours, separately, and then exposed to dexamethasone for an additional 6 hours. Crude extracts from control, dexamethasone and fluoxetine-treated C6 glioma cells were separated on a 10% SDS-PAGE and probed with anti-HSP70 mAb. RESULTS: 1) Dexamethasone (10 uM, 6 hours) reduced the level of HSP70 expression relative to control, but this reduction was not statistically significant. 2) Pretreatment with fluoxetine (10 uM, 1, 6, 24, and 72 hours) and exposure to dexamethasone (10 uM, 6 hours) decreased the level of HSP70 expression according to the duration of fluoxetine treatment. 3) Fluoxetine significantly reduced the level of HSP70 at 24 and 72 hours compared to control. However, compare to the level of HSP70 expression at 24 hours, the level of HSP70 expression at 72 hours was elevated. CONCLUSION: These findings suggest that dexamethasone and fluoxetine may affect HSP70 expression through effects on GR.

Fluoxetine Pretreatment Exert Time-Dependent Inhibits the Dexamethasone-Mediated Heat Shock Protein 70 Expression in Rat C6 Glioma Cells / 대한정신약물학회지

OBJECTIVE: The aim of this study was to examine the effect of dexamethasone and fluoxetine on the expression of 70 kDa heat shock protein (HSP70) in C6 glioma cells. METHODS: The C6 glioma cells belong to control group were incubated with DMEM culture solution, the cells belong to dexamethasone group were incubated with dexamethasone for 6 hours, and the cells belong to fluoxetine group were incubated with fluoxetine for 1, 6, 24, and 72 hours, separately, and then exposed to dexamethasone for an additional 6 hours. Crude extracts from control, dexamethasone and fluoxetine-treated C6 glioma cells were separated on a 10% SDS-PAGE and probed with anti-HSP70 mAb. RESULTS: 1) Dexamethasone (10 uM, 6 hours) reduced the level of HSP70 expression relative to control, but this reduction was not statistically significant. 2) Pretreatment with fluoxetine (10 uM, 1, 6, 24, and 72 hours) and exposure to dexamethasone (10 uM, 6 hours) decreased the level of HSP70 expression according to the duration of fluoxetine treatment. 3) Fluoxetine significantly reduced the level of HSP70 at 24 and 72 hours compared to control. However, compare to the level of HSP70 expression at 24 hours, the level of HSP70 expression at 72 hours was elevated. CONCLUSION: These findings suggest that dexamethasone and fluoxetine may affect HSP70 expression through effects on GR.

The Effects of Venlafaxine on Neurite Growth of PC12 Cells

OBJECTIVES: The purpose of this study is to examine the effects of venlafaxine, one of novel antidepressant drugs, on neurite growth in PC12 cells. METHODS: PC12 cells were cultured with NGF for eight days. Then different concentrations(0micrometer, 1micrometer, 5micrometer) of venlafaxine were mixed with cultured PC12 cells. After 24 hours and 48 hours of culture, we compared the effects of venlafaxine on the total length of neurites of cultured PC12 cells between no venlafaxine treated group(0micrometer) and venlafaxine treated groups(1micrometer and 5micrometer). Additionally, we studied the concentration-dependent effect of venlafaxine on differentiation in PC12 cells. RESULTS: Experimental results showed that 1) the mean length of neurites in 1micrometer and 5micrometer venlafaxine treated group was more increased than no venlafaxine treated group(p=0.002). 2) the length of neurite in 5micrometer venlafaxine treated group was more elongated than 1micrometer venlafaxine treated group(p=0.046). 3) the length of neurite in 6micrometer venlafaxine treated group was more elongated than all the other concentrations in our experiment. Above 6micrometer, the length of neurite was shortened in inverse proportion to the concentration of venlafaxine. CONCLUSIONS: This results suggest that venlafaxine, one of novel antidepressant drugs, promotes the differentiation of neuron. This study is believed to be a first step toward understanding the molecular and cellular mechanisms of antidepressant treatment.

Association of Serotonin Transporter Gene Polymorphism with Alcohol Dependence

OBJECTIVE: Under the hypothesis that 5-HTTLPR polymorphism plays some role in the susceptibility or vulnerability of some subgroup of alcohol dependence, associations of 5-HTTLPR polymorphism with alcohol dependence were examined. METHOD: This association analysis included 109 Korean alcohol dependent and 113 Korean control subjects. DNA of all subjects were genotyped for the biallelic functional polymorphism in the 5-HTTLPR. Considering the likelihood of heterogeneity in the alcohol dependence phenotype, alcohol dependent subjects were subgrouped by onset age, family history of alcohol dependence and severity of withdrawal symptoms. RESULTS: There were no significant differences in the frequencies of either the 5-HTTLPR genotype or the short vs. long allele in alcohol dependent and control subjects. The frequency of the S allele and S-carrier (LS or SS genotype) was significantly increased in the early onset alcohol dependent subjects and the familial alcohol dependent subjects compared with that in the control subjects. CONCLUSION: The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased susceptibility or vulnerability to develop early onset alcohol dependence and familial alcohol dependence, which characterize Cloninger's type 2 alcohol dependence.