Asymmetric expression of melatonin receptor mRNA in bilateral paravertebral muscles in adolescent idiopathic scoliosis.
ABSTRACT Comparison of melatonin receptor mRNA expression in bilateral paravertebral muscles in adolescent idiopathic scoliosis (AIS). OBJECTIVES.: To investigate the change of melatonin receptor mRNA expression in bilateral paravertebral muscles in AIS, congenital scoliosis (CS), and control in order to analyze its association to the pathogenesis of AIS.
Muscle imbalance and asymmetry of stretch receptors in the paravertebral muscles of patients with AIS were supposed to have a large role to play in the development and production of the deformity. Melatonin is a focus of studies of the mechanism underlying the development of scoliosis, and there is no research on the expression of melatonin receptors in the paravertebral muscles of patients with AIS.
Twenty cases with average age of 15.1 +/- 2.2 years and average Cobb angle of 56.2 degrees +/- 16.1 degrees, including 10 cases with Cobb angle >50 degrees and 10 cases with Cobb angle < or =50 degrees, were included in AIS group. The apical vertebrae were from T6 to T11. Twelve cases with an average age of 11.6 +/- 3.2 years and average Cobb angle of 59.2 degrees +/- 33.3 degrees were included in CS group. The apical vertebrae were from T7 to T12. Ten cases without scoliosis were in the control group. The mRNA expression of melatonin receptor subtype MT1 and MT2 was detected by the RT-PCR method.
The MT2 mRNA expression on the concave side of the paravertebral muscle was higher than that on the convex side in AIS and CS groups (P < 0.05), but the MT1 mRNA expression showed no significant difference (P > 0.05). In the AIS group, the ratio of MT2 mRNA expression on the concave side compared with the convex side in cases with Cobb angle >50 degrees and cases with Cobb angle < or =50 degrees showed no significant difference (P > 0.05). The MT1 and MT2 mRNA expression showed no significant difference in control group (P > 0.05).
The melatonin receptor expression in bilateral paravertebral muscles in AIS is asymmetric, which may be a secondary change. The bilateral asymmetry in force exerted on the scoliotic spine may be the cause.
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ABSTRACT: Comparative genomic hybridization (CGH) microarrays. To identify genomic copy number variations (CNVs) in degenerative lumbar scoliosis (DLS) patients, and investigate the possibility of genetic predisposition in DLS. Genome scanning technology enables search for presence of CNVs. CGH microarray is a useful procedure in a genome-wide study. Among 45 consecutive patients who were diagnosed as DLS, 15 patients who manifested greatest Cobb's angle were selected for the array-CGH based CNV analysis. Control group was blood samples from 58 individuals without DLS. Oligonucleotide CGH microarray was utilized to analyze the CNV. Gene searches were performed for CNV DNA with significant gene-dosage difference. Validation qualitative PCR(qPCR) was performed at 3 genetic loci: at chromosome 2--TMEM163 gene, at chromosome 16--ANKRD 11 gene, and at chromosome 18--NFATC1 gene. Genomic gains and losses were observed using the oligonucleotide CGH microarray. Identified CNVs were 446 ± 129 per individual. Gain- and loss-CNVs were identified as 196 ± 24 and 250 ± 110, respectively. The length of total CNV per individual was 30,946,730 ± 31,658,175 bp, and mean CNV-length was 61,017 ± 40,620 (median length 6411 ± 1994). Comparison with control group revealed 260 CNVs, which were significant (P < 10(-3)). Validation qPCR for gene-dosage comparison of DLS group DNA versus control group DNA in TMEM163 (P < 0.001); ANKRD 11 (P = 0.000); and NFATC1 (P = 0.000) gene showed significant difference. Various whole-genome CNVs specific to DLS patients were observed. Validation qPCR confirmed significantly different gene-dosages for TMEM163, ANKRD 11, and NFATC1 genes. We consider that the expression of DLS is supported by various typical CNV-associated structural variants of the genome.Spine 05/2011; 36(21):1782-93. · 2.16 Impact Factor
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ABSTRACT: Major Depressive Disorder (MDD) is an extremely disabling, chronic and recurrent disease. Moreover, subthreshold depressive symptoms often persist during periods of apparent remission. Such symptoms include sleep disturbances, sexual dysfunction, weight gain, fatigue, disinterest, anxiety, and/or emotional blunting, which do not often respond to available antidepressant treatments. Agomelatine is a melatonergic agonist (at both MT1 and MT2 receptors) and serotonin 2C (5-HT2C) receptor antagonist. Agomelatine should be particularly useful in the treatment of MDD because of its unique pharmacological profile, accounting for its effective antidepressant action with a relative lack of serious adverse effects. Several clinical trials confirmed the antidepressant efficacy of agomelatine in patients with MDD, with significant efficacy even in severe manifestations of disease and on residual subtreshold symptoms. This compound showed a relative early onset of action as well as an excellent safety and tolerability profile linked to a low discontinuation rate in MDD patients. Moreover, some data suggest that agomelatine has not only antidepressant effects but also anxiolytic effects, with a potential benefit both on anxiety symptoms associated with MDD and in the treatment of generalised anxiety disorder. This review will summarise the role of the melatonergic system in MDD and will describe the characteristics of agomelatine, focusing on its efficacy and safety in the treatment of MDD.CNS & neurological disorders drug targets 02/2011; 10(1):119-32. · 3.57 Impact Factor
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ABSTRACT: The cause of adolescent idiopathic scoliosis (AIS) in humans remains obscure and probably multifactorial. At present, there is no proven method or test available to identify children or adolescent at risk of developing AIS or identify which of the affected individuals are at risk of progression. Reported associations are linked in pathogenesis rather than etiologic factors. Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis), but at present, the data available cannot clearly show the role of melatonin in producing scoliosis in humans. The data regarding human melatonin levels are mixed at best, and the melatonin deficiency as a causative factor in the etiology of scoliosis cannot be supported. It will be an important issue of future research to investigate the role of melatonin in human biology, the clinical efficacy, and safety of melatonin under different pathological situations. Research is needed to better define the role of all factors in AIS development.European Spine Journal 03/2011; 20 Suppl 1:S68-74. · 2.47 Impact Factor