Prenatal Immune Challenge in Mice Leads to Partly Sex-Dependent Behavioral, Microglial, and Molecular Abnormalities Associated with Schizophrenia

Epidemiological studies revealed that environmental factors comprising prenatal infection are strongly linked to risk for later development of neuropsychiatric disorders such as schizophrenia. Considering strong sex differences in schizophrenia and its increased prevalence in males, we designed a methodological approach to investigate possible sex differences in pathophysiological mechanisms. Prenatal immune challenge was modeled by systemic administration of the viral mimic polyinosinic-polycytidylic acid (Poly I:C) to C57BL/6 mice at embryonic day 9.5. The consequences on behavior, gene expression, and microglia—brain immune cells that are critical for normal development—were characterized in male vs. female offspring at adulthood. The cerebral cortex, hippocampus, and cerebellum, regions where structural and functional alterations were mainly described in schizophrenia patients, were selected for cellular and molecular analyses. Confocal and electron microscopy revealed most pronounced differences in microglial distribution, arborization, cellular stress, and synaptic interactions in the hippocampus of male vs. female offspring exposed to Poly I:C. Sex differences in microglia were also measured under both steady-state and Poly I:C conditions. These microglial alterations were accompanied by behavioral impairment, affecting for instance sensorimotor gating, in males. Consistent with these results, increased expression of genes related to inflammation was measured in cerebral cortex and hippocampus of males challenged with Poly I:C. Overall, these findings suggest that schizophrenia's higher incidence in males might be associated, among other mechanisms, with an increased microglial reactivity to prenatal immune challenges, hence determining disease outcomes into adulthood

Reboxetina no tratamento da bulimia nervosa Reboxetine in the treatment of bulimia nervosa

É vasta a literatura demonstrando a eficácia dos antidepressivos inibidores seletivos da recaptação de serotonina na Bulimia Nervosa, diminuindo a freqüência do comportamento alimentar compulsivo e dos vômitos. A boa resposta terapêutica aos agentes farmacológicos noradrenérgicos, como a desipramina e a reboxetina, embora menos encontrada na literatura, também já foi documentada. O presente relato de caso descreve o tratamento de uma paciente com Bulimia Nervosa utilizando-se reboxetina na dose de 4 a 8 mg ao dia. A resposta terapêutica vem confirmar os resultados favoráveis do uso desta droga no tratamento da Bulimia Nervosa.<br>There is a substancial body of literature demonstrating the efficacy of selective serotonin reuptake inhibitors antidepressants (SSRI) in reducing binge eating and vomiting frequency in Bulimia Nervosa. Good therapeutic response to noradrenergic agents, like desipramine and reboxetine, though not frequently reported in literature, has already been demonstrated. This case report describes the treatment of Bulimia Nervosa with reboxetine (4 to 8 mg/day) and its favorable therapeutic results