Neurogenesis in the R6/2 mouse model of Huntington's disease is impaired at the level of NeuroD1.

Adult neurogenesis is impaired in the hippocampus of transgenic R6 mouse models of Huntington's disease (HD). The phenotypes of R6 transgenic mice mimic several symptoms and signs of the disease (Li et al., 2005). They exhibit neurological and endocrine changes resembling some symptoms seen in humans. The reduction in neurogenesis is only apparent in the dentate gyrus as the number of newborn neurons in the subventricular zone, and olfactory bulb, is normal in R6 mice. The mechanism(s) underlying the reduction in hippocampal neurogenesis is still not fully understood. Here we show that the number of neuroblasts, but not granule neuron progenitors, is greatly reduced in 11-week old transgenic mice compared with wild-type (WT) controls. We demonstrate that NeuroD1 expression is reduced in the hippocampus. This is coupled to a decreased expression of downstream markers doublecortin and calretinin in maturing neurons. Taken together, our results suggest that mutant huntingtin (Htt) causes alterations of proteins expression in hippocampal progenitors, which might contribute to cognitive deficits in Huntington's disease.

Fibroblast growth factor signaling is required for the proliferation and patterning of progenitor cells in the developing anterior pituitary.

The proliferation and patterning of progenitor cells in the anterior pituitary require signals derived from the neuroepithelium of the juxtaposed infundibulum. The infundibulum expresses Fibroblast growth factor (Fgf) 8 and Fgf 18, and FGFs can mimic some of the activities of the infundibulum. The requirement for FGF signaling during growth and patterning of the anterior pituitary has not, however, been established. By blocking FGF receptor signaling in explants of the anterior pituitary cultured in vitro we provide evidence that FGF signaling derived from the infundibulum is required for the proliferation and patterning of progenitor cells in the anterior pituitary.

Umbilical artery waveform analysis and biophysical profile. A comparison of two methods to identify compromised fetuses.

Sixty-nine singleton high-risk pregnancies were assessed with both umbilical artery flow velocity waveform analysis and fetal biophysical profile within 10 days of delivery. An abnormal outcome, as defined as either small for gestational age at birth (SGA) or fetal distress during labour, was found in 30 babies. The peak systolic/end diastolic (A/B) ratio from the umbilical artery had a higher sensitivity (37%), specificity (92%), positive predictive value (79%) and negative predictive value (66%) than the fetal biophysical profile (27%, 82%, 53%, and 59%, respectively) in the diagnosis of abnormal outcome. Additional information from a real-time ultrasound assessment, such as the diagnosis of malformations and oligohydramnios could justify a combination of the two methods in antenatal monitoring of high-risk pregnancies.

Mothering problems and child morbidity amongst "mothers with emotional disturbances".

In a study of 1,955 primigravidae who gave birth to a live singleton baby, 227 (11.6%) scored 'positive' (7+) in an antenatal Health Questionnaire enquiring into pre-pregnancy emotional disturbances. This group of mothers had more frequent depression, and this was of longer duration after their delivery compared with those scoring less than 7 (less than or equal to 6). Those scoring 7+ were less likely to breast-feed and the infants were more often ill during the first year of life. There were also differences in 'minor obstetric complications' between the two survey groups. This suggests that the application of this Health Questionnaire antenatally can identify emotionally vulnerable women, who could benefit from support and education during the antenatal period.

Antenatal health questionnaire to identify "mothers with emotional disturbances" as a potential risk group.

An important task in antenatal care is to identify mothers at risk during pregnancy, with the aim of minimizing morbidity and mortality. This paper describes the outcome of a health questionnaire distributed antenatally to 2086 primigravidae during the Tayside Infant Morbidity and Mortality Study 1980-81. The aim of this study was to test a health questionnaire, known to identify mothers with emotional disturbances, and investigate the outcome of their pregnancies. Two hundred and thirty-eight mothers (11.4%) had a 'positive' score in this study. This rather small group of women had a significantly higher incidence of psycho-social risk factors. The questionnaire return rate was high, more than 99%, suggesting that such a questionnaire could be used as a screening instrument to identify 'risk mothers'.