RESUMO
Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.
Assuntos
Núcleo Caudado , Vias Neurais/fisiopatologia , Núcleo Accumbens , Transtorno Obsessivo-Compulsivo/fisiopatologia , Putamen , Transcriptoma , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Núcleo Caudado/metabolismo , Núcleo Caudado/fisiopatologia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiopatologia , Putamen/metabolismo , Putamen/fisiopatologiaAssuntos
Tumores do Estroma Gastrointestinal/genética , Melanoma/genética , Neoplasias Cutâneas/genética , Proteína X Associada a bcl-2/genética , Cromossomos Humanos Par 19 , Tumores do Estroma Gastrointestinal/patologia , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Melanoma/patologia , Pessoa de Meia-Idade , Linhagem , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: The transverse rectus abdominis musculocutaneous (TRAM) flap may develop necrosis, especially in patients with risk factors such as previous abdominoplasty, caused by damage to perforating vessels during surgical procedures. This study was designed from the perspective of using vascular endothelial growth factor (VEGF) gene therapy with plasmid vector after abdominoplasty to stimulate neovascularization of the TRAM flap, thus increasing flap viability. METHODS: Thirty-two Wistar rats were divided into four groups (n = 8). A right inferiorly based TRAM flap was constructed in all animals and was the only procedure performed in group I (TRAM flap). Animals from groups II (abdominoplasty) and III (plasmid) underwent abdominoplasty and were injected intramuscularly with physiologic saline solution and empty plasmid, respectively. Group IV (VEGF) received intramuscular injection of naked plasmid DNA encoding VEGF-165 during abdominoplasty. The TRAM flap was created 30 days after abdominoplasty. RESULTS: The mean necrosis was 24.65 +/- 18.13 percent in group I, 62.49 +/- 28.06 percent in group II, 57.80 +/- 25.43 percent in group III, and 18.33 +/- 16.20 percent in group IV. The number of vessels in the TRAM flap was determined by immunohistochemistry using the antibody human heart factor. Groups I and IV had a similar number of vessels, as did groups II and III. Groups I and IV had greater viability and number of vessels than groups II and III. CONCLUSION: VEGF gene therapy increased viability and vessel number in the TRAM flap created after abdominoplasty in a rat model.