RESUMO
Prenatal exposure to alcohol causes a wide range of deficits known as fetal alcohol spectrum disorders (FASDs). Many factors determine vulnerability to developmental alcohol exposure including timing and pattern of exposure, nutrition and genetics. Here, we characterized how a prevalent single nucleotide polymorphism in the human brain-derived neurotrophic factor (BDNF) gene (val66met) modulates FASDs severity. This polymorphism disrupts BDNF's intracellular trafficking and activity-dependent secretion, and has been linked to increased incidence of neuropsychiatric disorders such as depression and anxiety. We hypothesized that developmental ethanol (EtOH) exposure more severely affects mice carrying this polymorphism. We used transgenic mice homozygous for either valine (BDNFval/val ) or methionine (BDNFmet/met ) in residue 68, equivalent to residue 66 in humans. To model EtOH exposure during the second and third trimesters of human pregnancy, we exposed mice to EtOH in vapor chambers during gestational days 12 to 19 and postnatal days 2 to 9. We found that EtOH exposure reduces cell layer volume in the dentate gyrus and the CA1 hippocampal regions of BDNFmet/met but not BDNFval/val mice during the juvenile period (postnatal day 15). During adulthood, EtOH exposure reduced anxiety-like behavior and disrupted trace fear conditioning in BDNFmet/met mice, with most effects observed in males. EtOH exposure reduced adult neurogenesis only in the ventral hippocampus of BDNFval/val male mice. These studies show that the BDNF val66met polymorphism modulates, in a complex manner, the effects of developmental EtOH exposure, and identify a novel genetic risk factor that may regulate FASDs severity in humans.
Assuntos
Ansiedade/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Hipocampo/efeitos dos fármacos , Mutação de Sentido Incorreto , Efeitos Tardios da Exposição Pré-Natal/genética , Animais , Condicionamento Clássico , Medo , Feminino , Hipocampo/crescimento & desenvolvimento , Masculino , Camundongos , Polimorfismo de Nucleotídeo Único , GravidezRESUMO
Most instruments intended for luminescence spectroscopy fall in the category of uncorrected spectrofluorimeters. In many routine analyses, uncorrected spectra are useful, especially if they do not have to be compared with others from different laboratories. However, for theoretical work, results must be on an absolute basis. This paper describes a method and the related equipment that have been developed and used to obtain, on an absolute basis, many of the parameters that are important in photochemical research. The system can provide absolute emission spectra, absolute excitation spectra, and quantum efficiencies for luminescence, fluorescence, delayed fluorescence, and phosphorescence. Also, it can measure the half-life of phosphorescence and of delayed fluorescence. Provision is made for the independent and continuous control of the time between excitation and detection pulses, thus allowing the measurement of the half-life at any wavelength of emission. With these provisions it is possible to resolve overlapping fluorescence, delayed fluorescence, and phosphorescence spectra.
