RESUMEN
Anorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using genome-wide methods, recent studies have associated many genes with the disorder. We characterized these genes by projecting them into reference transcriptomic atlases of the prenatal and adult human brain to determine where these genes are expressed in fine detail. We found that genes from an induced stem cell study of anorexia nervosa cases are expressed at higher levels in the lateral parabrachial nucleus. Although weaker, expression enrichment of the adult lateral parabrachial is also found with genes from independent genetic studies. Candidate causal genes from the largest genetic study of anorexia nervosa to date were enriched for expression in the arcuate nucleus of the hypothalamus. We also found an enrichment of anorexia nervosa associated genes in the adult and fetal raphe and ventral tegmental areas. Motivated by enrichment of these feeding circuits, we tested if these genes respond to fasting in mice hypothalami, which highlighted the differential expression of Rps26 and Dalrd3. This work improves our understanding of the neurobiology of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.
Asunto(s)
Anorexia Nerviosa/genética , Perfilación de la Expresión Génica , Transcriptoma , Adulto , Animales , Encéfalo/metabolismo , Exoma , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Hipotálamo/metabolismo , Células Madre Pluripotentes Inducidas/citología , Masculino , Ratones , Microglía/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Ribosómicas/genética , ARNt Metiltransferasas/genéticaRESUMEN
Human induced pluripotent stem cells (iPSCs) represent a revolutionary tool for disease modeling and drug discovery. The generation of tissue-relevant cell types exhibiting a patient's genetic and molecular background offers the ability to develop individual and effective therapies. In this review, we present some major achievements in the neuroscience field using iPSCs and discuss promising perspectives in personalized medicine. In addition to disease modeling, the understanding of the cellular and molecular basis of neurological disorders is explored, including the discovery of new targets and potential drugs. Ultimately, we highlight how iPSC technology, together with genome editing approaches, may bring a deep impact on pre-clinical trials by reducing costs and increasing the success of treatments in a personalized fashion.
Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Células Madre Embrionarias , Edición Génica/métodos , Células Madre Pluripotentes Inducidas , Modelos Neurológicos , Enfermedades del Sistema Nervioso , Medicina de Precisión/métodos , Humanos , Enfermedades del Sistema Nervioso/terapiaRESUMEN
Chlorophyllin, a sodium-copper salt derivative of chlorophyll-a and -b, was evaluated for antimutagenic activity against ethyl methane sulfonate by the hypoxanthin-guanine-phosphoribosyl transferase (HGPRT) assay. The results obtained suggest that this chlorophyllin can potentiate the mutagenicity of an alkylating agent which induces DNA damage.