Pre-B-cell colony-enhancing factor (PBEF/Visfatin) gene expression is modulated by NF-kappaB and AP-1 in human amniotic epithelial cells.

A localized intrauterine inflammatory response is often associated with the initiation of normal human parturition, whereas infection causes a similar but more florid response initiating preterm labor. Pre-B-cell colony-enhancing factor (PBEF) is expressed in the human fetal membranes and is up-regulated by labor, severe infection and inflammatory stimuli. The aim of this study was to determine the involvement of the transcription factors NF-kappaB and AP-1 in the response of PBEF to an inflammatory stimulus and compare it with IL-8. The results showed that this treatment of amniotic epithelial-like cells (WISH) and primary amniotic epithelial cells increased expression of PBEF and IL-8, but IL-8 responded 100-fold more than PBEF. IL-1beta treatment together with a panel of NF-kappaB and AP-1 inhibitors demonstrated the involvement of these transcription factors in the up-regulation of PBEF. These data show that an inflammatory stimulus in the fetal membranes inducing NF-kappaB and AP-1 would up-regulate PBEF as well as IL-8.

Ultrastructural and behavioural changes precede amyloid deposition in a transgenic model of Alzheimer's disease.

We describe the thorough characterisation of a new transgenic mouse line overexpressing the 695-amino acid isoform of human amyloid precursor protein harbouring the Swedish double familial Alzheimer's disease mutation. This line, referred to as TAS10, exhibits neuropathological features and cognitive deficits that are closely correlated to the accumulation of Abeta in their brain and that are reminiscent of those observed in AD. Data on the TAS10 line are presented at five time points: 2, 6, 12, 18 and 24 months in a longitudinal study. The TAS10 line is characterised by the following changes: i) significant age-related increases in the levels of total and individual species (1-40, 1-42) of beta-amyloid in the brains of transgenics compared with non-transgenic littermates; ii) transgenic mice showed pronounced spatial learning deficits in the Morris water maze at 6 months and working memory deficits by 12 months; iii) amyloid plaque and associated pathologies were observed by the 12-month time point and the burden increased substantially, particularly in the cortex, by 18 months; iv) electron microscopy of the hippocampus of transgenic mice showed evidence of abnormal ultrastructural features such as dystrophic neurites and lipid deposits that developed from 6 months and increased in number and severity with age. Morphometric studies demonstrate that the synapse to neuron ratio is higher in transgenics than in control mice at 12 months, but this ratio decreases as they age and synapse size increases. Thus, this mouse model exhibits a close correlation of amyloid burden with behavioural deficits and ultrastructural abnormalities and so represents an ideal system to study the mechanisms underlying the impact of amyloid pathology on CNS function.