T‐lymphocyte‐induced,fas‐mediated apoptosis is associated with early keratinocyte differentiation

Please cite this paper as: T‐lymphocyte‐induced, fas‐mediated apoptosis is associated with early keratinocyte differentiation. Experimental Dermatology 2009. Abstract: The development of eczematous lesions is thought to be due in part to a breakdown in skin barrier function as a result of T lymphocytes (T cells) invading the skin causing epidermal keratinocyte apoptosis. In this study, we investigated the interaction of T cells and keratinocytes on apoptosis and terminal differentiation using an in vitro co‐culture system. Experiments were performed using the HaCaT keratinocyte cell line or normal human epidermal keratinocytes. Activated human peripheral blood‐derived T cells were found to induce Fas‐dependent keratinocyte apoptosis by up to sixfold. Increased Fas was associated with increased IFN‐γ. The T‐cell apoptotic signal was found to target preferentially keratinocytes in the very early stages of terminal differentiation, such as those with low levels of α6‐integrin expression, and result in subsequent increased caspase 3 activity. This observation was accompanied by a marked increase in keratinocyte ICAM‐1 expression and its ligand LFA‐1 on T cells. Our data suggest that T cells may initiate the onset of keratinocyte terminal differentiation making them more susceptible to Fas‐dependent cell death signals delivered by the T cells.     

Temporal-Spatial Profiling of Pedunculopontine Galanin-Cholinergic Neurons in the Lactacystin Rat Model of Parkinson’s Disease

Parkinson’s disease (PD) is conventionally seen as resulting from single-system neurodegeneration affecting nigrostriatal dopaminergic neurons. However, accumulating evidence indicates multi-system degeneration and neurotransmitter deficiencies, including cholinergic neurons which degenerate in a brainstem nucleus, the pedunculopontine nucleus (PPN), resulting in motor and cognitive impairments. The neuropeptide galanin can inhibit cholinergic transmission, while being upregulated in degenerating brain regions associated with cognitive decline. Here we determined the temporal-spatial profile of progressive expression of endogenous galanin within degenerating cholinergic neurons, across the rostro-caudal axis of the PPN, by utilizing the lactacystin-induced rat model of PD. First, we show progressive neuronal death affecting nigral dopaminergic and PPN cholinergic neurons, reflecting that seen in PD patients, to facilitate use of this model for assessing the therapeutic potential of bioactive peptides. Next, stereological analyses of the lesioned brain hemisphere found that the number of PPN cholinergic neurons expressing galanin increased by 11%, compared to sham-lesioned controls, and increasing by a further 5% as the neurodegenerative process evolved. Galanin upregulation within cholinergic PPN neurons was most prevalent closest to the intra-nigral lesion site, suggesting that galanin upregulation in such neurons adapt intrinsically to neurodegeneration, to possibly neuroprotect. This is the first report on the extent and pattern of galanin expression in cholinergic neurons across distinct PPN subregions in both the intact rat CNS and lactacystin-lesioned rats. The findings pave the way for future work to target galanin signaling in the PPN, to determine the extent to which upregulated galanin expression could offer a viable treatment strategy for ameliorating PD symptoms associated with cholinergic degeneration.     

The Dutch Claustrophobia Questionnaire: Psychometric properties and predictive validity

Fear of suffocation and fear of restriction are thought to underlie claustrophobia and can be assessed with the Claustrophobia Questionnaire (CLQ; Radomsky et al., 2001). A first study tested the psychometric properties of a Dutch version of the CLQ. Students (N = 363) completed a Dutch translation of the CLQ and a set of other questionnaires assessing other specific fears, anxiety or depression. Results confirmed the two-factor structure and showed that the Dutch version of the CLQ has good psychometric properties. A second study tested the predictive validity of the Dutch CLQ. Participants (N = 23) were exposed each to nine claustrophobic situations with elements of suffocation, restriction or both. The Dutch CLQ was found to be a significant predictor of fear and respiratory reactivity during claustrophobic exposure. It can be concluded that the Dutch version of the CLQ is a reliable and valid instrument to assess claustrophobic fear.