RESUMEN
Zinc is highly concentrated in synaptic vesicles throughout the mammalian telencephalon and, in particular, the hippocampal dentate gyrus. A role for zinc in modulating synaptic plasticity has been inferred, but whether zinc has a particular role in experience-dependent plasticity has yet to be determined. The aim of the current study was to determine whether vesicular zinc is important for modulating adult hippocampal neurogenesis in an experience-dependent manner and, consequently, hippocampal-dependent behaviour. We assessed the role of vesicular zinc in modulating hippocampal neurogenesis and behaviour by comparing ZnT3 knockout (KO) mice, which lack vesicular zinc, to wild-type (WT) littermates exposed to either standard housing conditions (SH) or an enriched environment (EE). We found that vesicular zinc is necessary for a cascade of changes in hippocampal plasticity following EE, such as increases in hippocampal neurogenesis and elevations in mature brain-derived neurotrophic factor (mBDNF), but was otherwise dispensable under SH conditions. Using the Spatial Object Recognition task and the Morris Water task we show that, unlike WT mice, ZnT3 KO mice showed no improvements in spatial memory following EE. These experiments demonstrate that vesicular zinc is essential for the enhancement of adult hippocampal neurogenesis and behaviour following enrichment, supporting a role for zincergic neurons in contributing to experience-dependent plasticity in the hippocampus.
Asunto(s)
Hipocampo , Zinc , Ratones , Animales , Hipocampo/fisiología , Vesículas Sinápticas , Neuronas , Ratones Noqueados , Neurogénesis/fisiología , MamíferosAsunto(s)
Nocardiosis/diagnóstico , Nocardiosis/tratamiento farmacológico , Adulto , Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Biopsia , Diagnóstico Diferencial , Diagnóstico por Imagen , Quimioterapia Combinada , Cefalea/diagnóstico , Humanos , Imipenem/uso terapéutico , Masculino , Exposición Profesional , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoAsunto(s)
Exantema/etiología , Lupus Eritematoso Cutáneo/diagnóstico , Dolor/etiología , Exantema/patología , Femenino , Humanos , Lupus Eritematoso Cutáneo/complicaciones , Lupus Eritematoso Cutáneo/patología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/patología , Dolor/patología , Piel/patología , Adulto JovenRESUMEN
BACKGROUND: The objective of this study was to review changes in the prevalence of opioid use disorder in pregnancy, and to describe the prenatal care and neonatal outcomes following the implementation of buprenorphine treatment at a large US obstetrical clinic during the on-going opioid epidemic. METHODS: We conducted a retrospective cohort study of 310 women (332 pregnancies) with opioid use disorders and their neonates delivered between June 2006 and December 2010 at an obstetrical clinic in the US. Trends in patient volume, characteristics and outcomes by calendar year were assessed using the Cochran-Armitage test and linear regression. RESULTS: There was an almost two-fold increase in the volume of pregnant women treated annually from 2006 through 2010. Most women were treated with methadone (74%), with buprenorphine becoming more common over calendar time: 3.0% in 2006 to 41% in 2010. The mean dose of buprenorphine at delivery was: 11.4 mg in 2007, 14.1 mg in 2008, 14.1 mg in 2009, and 16.8 mg in 2010; an average increase of 2.1 mg year. There were no differences in mean methadone dose over time. From 2006 to 2010 there were increases in the prevalence of prescribed concomitant psychotropic medications and vaginal deliveries, and in the proportion of neonates treated pharmacologically for neonatal abstinence syndrome (NAS). NAS pharmacologic management also varied by calendar year with more use of neonatal morphine and clonidine in later years. CONCLUSIONS: The number of mother-infant pairs increased significantly from 2006 to 2010 and the clinical characteristics of these patients changed over time. Our experience reflects the rising increase in opioid use disorders in pregnancy and NAS, mandating the need for expansion of comprehensive prenatal care options for these women and their children.
Asunto(s)
Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Atención Prenatal/métodos , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Síndrome de Abstinencia Neonatal/prevención & control , Embarazo , Estudios Retrospectivos , Medición de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Injury of the brain is a leading cause of long-term disability. Recent evidence indicates that the selective serotonin reuptake inhibitor drug fluoxetine may be beneficial when administered following brain injury. However, its potential to promote recovery and the mechanisms by which it might do so require further characterization. In the present experiment, fluoxetine was administered to mice for 4 weeks following injury of medial frontal cortex (MFC). MFC injury altered behavior, reducing locomotion, decreasing swim speed in the Morris water task, and decreasing anxiety-like behavior in the elevated plus maze. Fluoxetine treatment did not affect these behavioral alterations, but it did increase the social dominance of the injured mice, as assessed by the tube test. Fluoxetine treatment also hastened learning of a T-maze position discrimination task, independently of lesion condition. Anatomically, fluoxetine failed to decrease lesion size, increase the survival of cells born 1-week post injury in the hippocampal dentate gyrus, or reverse the reduction in spine density in layer II/III pyramidal neurons in cingulate cortex caused by the lesions. Fluoxetine did, however, increase the dendritic arborization of these cells, which was reduced in the mice with lesions. Thus, while not all the effects of MFC injury were ameliorated, the behavioral outcome of mice with MFC injuries was improved, and one of the neuroanatomical sequelae of the lesions counteracted, by chronic fluoxetine, further contributing to the evidence that fluoxetine could be a useful treatment following brain injury.