Biomedical subjects

Mao-Liang Chen

Publications and source records attributed to Mao-Liang Chen.

6 recordsLinked to original sources

PubMed2006

A complete genetic association scan of the 22q11 deletion region and functional evidence reveal an association between DGCR2 and schizophrenia.

Several lines of evidence have established the presence of an association between a 3-Mb deletion in chromosome 22q11 and schizophrenia. In this paper we present a complete high-density SNP scan of this segment using DNA pools, and demonstrate significant association between two distinct regions and schizophrenia in an Ashkenazi Jewish population. One of these regions contains the previously identified COMT gene. The pattern of association and linkage disequilibrium (LD) in the second region suggest that DGCR2, which encodes a putative adhesion receptor protein, is the susceptibility gene. We confirmed the association between DGCR2 and schizophrenia through individual genotyping of 1,400 subjects. In a gene expression analysis the risk allele of a coding SNP associated with schizophrenia was found to be associated with a reduced expression of DGCR2. Interestingly, the expression of DGCR2 was also found to be elevated in the dorsolateral prefrontal cortex of schizophrenic patients relative to matched controls. This increase is likely to be explained by exposure to antipsychotic drugs. To test that hypothesis, we looked at rats exposed to antipsychotic medication and found significantly elevated levels of DGCR2 transcripts. The genetic and functional evidences here reported suggest a possible role of the DGCR2 gene in the pathology of schizophrenia and also in the therapeutic effects of antipsychotic drugs.

Alleles↗

PubMed2005

Chronic antipsychotics treatment regulates MAOA, MAOB and COMT gene expression in rat frontal cortex.

Chronic antipsychotic drugs treatment may regulate the expression of a variety of genes in the brain, which may underscore their clinical efficacy and/or side effects. In this study, we measured the mRNA levels of three genes encoding the catabolic enzymes of biogenic amine neurotransmitters, i.e., monoamine oxidase A (MAOA), B (MAOB) and catechol O-methyltransferase (COMT), in rat frontal cortex following 4 weeks' treatment of various antipsychotic drugs using quantitative PCR. Significantly elevated mRNA levels of MAOB and COMT were first observed in frontal cortex of rats treated with risperidone (1mg/kg) when compared to control animals. Further study showed that chronic treatment of olanzapine (2mg/kg), but not haloperidol (1mg/kg) or clozapine (20mg/kg), resulted in significantly increased mRNA levels of MAOA, MAOB and COMT in rat frontal cortex as compared to control animals. These results indicate that chronic treatment of different antipsychotic drugs may differentially regulate the gene expression of three catabolic enzymes of biogenic amine neurotransmitters, and which may partly account for the molecular mechanism of their different clinical efficacy.

Animals↗

PubMed2005

Comparative proteome analysis revealed up-regulation of transthyretin in rat brain under chronic clozapine treatment.

Long-term administration of antipsychotic drugs can induce differential expression of various proteins in brain cells, which may underscore the molecular mechanism of their clinical efficacy and/or side effects. We used two-dimensional gel electrophoresis in combination with mass spectrometry to screen differentially expressed proteins in the brain cells of rats under chronic clozapine treatment. We identified a protein, transthyretin, which was significantly up-regulated in the hippocampus of rats after four weeks' treatment of clozapine (20mg/kg) as compared with control animals. Western blot analysis further supported this finding. Besides, we also observed increased transcription of transthyretin mRNA in the cerebral cortex of rats under chronic treatment of clozapine (20mg/kg) or olanzapine (2mg/kg), but not haloperidol (1mg/kg), using real-time quantitative PCR. Transthyretin is a retinol carrier protein, our findings suggest that antipsychotic drugs treatment may affect the retinoid signaling cascade in the brain. Besides, transthyretin is also an indicator of nutritional status; increased transthyretin may be associated with the body weight gain of taking atypical antipsychotic drugs. This study also demonstrates that comparative proteome analysis is a feasible method to study the molecular mechanism of chronic antipsychotic drugs treatment.

Animals↗

PubMed2005

Microarray analysis of differentially expressed genes in rat frontal cortex under chronic risperidone treatment.

Long-term administration of antipsychotic drugs can induce differential expression of a variety of genes in the brain, which may underscore the molecular mechanism of the clinical efficacy and/or side effects of antipsychotic drugs. We used cDNA microarray analysis to screen differentially expressed genes in rat frontal cortex under 4 weeks' treatment of risperidone (1 mg/kg). Using real-time quantitative PCR, we were able to verify eight genes, whose expression were significantly upregulated in rat frontal cortex under chronic risperidone treatment when compared with control animals. These genes include receptor for activated protein kinase C, amida, cathepsin D, calpain 2, calcium-independent receptor for alpha-latrotoxin, monoamine oxidase B, polyubiquitin, and kinesin light chain. In view of the physiological function of these genes, the results of our study suggest that chronic risperidone treatment may affect the neurotransmission, synaptic plasticity, and proteolysis of brain cells. This study also demonstrates that cDNA microarray analysis is useful for uncovering genes that are regulated by chronic antipsychotic drugs treatment, which may help bring new insight into the molecular mechanism of antipsychotic drugs.

Animals↗

PubMed2004

Elevated adrenomedullin mRNA in lymphoblastoid cells from schizophrenic patients.

Adrenomedullin (ADM) is a 52 amino acid peptide with multiple physiological functions and wide tissue distributions including brain. Recently, elevated plasma levels of ADM were found in patients with schizophrenia, bipolar affective disorder and autism, suggesting the involvement of ADM in the pathophysiology of mental diseases. Using real-time quantitative PCR, we compared the ADM mRNA levels in lymphoblastoid cell lines between schizophrenic patients and controls. Male but not female schizophrenia patients had 2- to 3-fold higher ADM mRNA levels than controls (p<0.01). Our data support that ADM may be associated with the pathophysiology of schizophrenia, although the cause of the association needs further study.

Adrenomedullin↗

PubMed2002

Association of risperidone treatment response with a polymorphism in the 5-HT(2A) receptor gene.

OBJECTIVE: This study investigated the effect of the 102-T/C polymorphism in the 5-HT(2A) receptor gene on risperidone efficacy. METHOD: One hundred Han Chinese patients with acutely exacerbated schizophrenia were given risperidone for up to 42 days. The patients were genotyped for 5-HT(2A) polymorphisms. Psychopathology was measured biweekly with the Positive and Negative Syndrome Scale while the patients were taking risperidone. Generalized estimating equation methods were used to analyze the effects of treatment duration, T/C genotypes, and other prognostic factors on Positive and Negative Syndrome Scale performance. RESULTS: Patients with the C/C genotype had lower total scores, negative subscale scores, and general psychopathology scores but not positive subscale scores on the Positive and Negative Syndrome Scale than patients with the 102-T/C genotype. Patients with the T/C and T/T genotypes had comparable total and subscale scores. The number of previous hospitalizations and the dose of risperidone also affected Positive and Negative Syndrome Scale total scores. CONCLUSIONS: These results suggest that variations in the 5-HT(2A) receptor gene may influence individual responses to risperidone.

Adult↗