We investigated the function of c-Jun in PC12 cells by transfecting them with a plasmid containing a c-Jun cDNA transcription cassette. Transfected cells expressed high levels of c-Jun mRNA and ...protein and demonstrated an increase in both AP-1 DNA binding and gene activation. The c-Jun over-expressing cells showed marked neurite outgrowth but no evidence of spontaneous cell death. In fact, c-Jun over-expressing cells were more resistant to okadaic acid-induced apoptosis. The process outgrowth was not indicative of a full neuronal differentiation response as the transfected PC12 cells did not display action potentials when examined with whole-cell patch-clamping. The phosphorylation of c-Jun on serine 73 appears to be important for this neurite sprouting effect as mutagenesis at this site reduced sprouting whereas a serine 63 mutant tended to increase sprouting. Thus, in PC12 cells c-Jun expression does not induce apoptosis, but rather functions as a neurite outgrowth and neuronal survival signal.
The present study evaluated the safety of and obtained preliminary data on the cognitive effects of
l-deprenyl and physostigmine in patients with Alzheimer's Disease. Seventeen outpatients with ...Alzheimer's Disease participated in a double-blind crossover study in which they received 4 weeks of
l-deprenyl at a dose of 10 mg p.o., q.d., and 4 weeks of placebo in random order. During both the
l-deprenyl and placebo periods, patients received cognitive assessments during physostigmine (0.5 mg) and placebo infusions separated by 2 days. The cognitive effects of these agents alone and in combination were measured with digit span, verbal fluency, list learning, praxis, delayed recall, and delayed recognition tasks. Fifteen patients completed the study. The two drugs, used alone or in combination, were safe and well tolerated. Analyses of variance demonstrated that neither physostigmine nor
l-deprenyl, whether given alone or in combination, significantly improved cognition, when compared with the double placebo condition.
Alzheimer's disease (AD) is characterized by a decline in cognitive function and accumulation of amyloid-beta peptide (Abeta) in extracellular plaques. Mutations in amyloid precursor protein (APP) ...and presenilins alter APP metabolism resulting in accumulation of Abeta42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Abeta40, the more prevalent Abeta peptide secreted by cells and a major component of cerebral Abeta deposits, is less clear. In this study, virally-mediated gene transfer was used to selectively increase hippocampal levels of human Abeta42 and Abeta40 in adult Wistar rats, allowing examination of the contribution of each to the cognitive deficits and pathology seen in AD.
Adeno-associated viral (AAV) vectors encoding BRI-Abeta cDNAs were generated resulting in high-level hippocampal expression and secretion of the specific encoded Abeta peptide. As a comparison the effect of AAV-mediated overexpression of APPsw was also examined. Animals were tested for development of learning and memory deficits (open field, Morris water maze, passive avoidance, novel object recognition) three months after infusion of AAV. A range of impairments was found, with the most pronounced deficits observed in animals co-injected with both AAV-BRI-Abeta40 and AAV-BRI-Abeta42. Brain tissue was analyzed by ELISA and immunohistochemistry to quantify levels of detergent soluble and insoluble Abeta peptides. BRI-Abeta42 and the combination of BRI-Abeta40+42 overexpression resulted in elevated levels of detergent-insoluble Abeta. No significant increase in detergent-insoluble Abeta was seen in the rats expressing APPsw or BRI-Abeta40. No pathological features were noted in any rats, except the AAV-BRI-Abeta42 rats which showed focal, amorphous, Thioflavin-negative Abeta42 deposits.
The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology in vivo, and demonstrate that whilst expression of Abeta42 alone is sufficient to initiate Abeta deposition, both Abeta40 and Abeta42 may contribute to cognitive deficits.
A health needs assessment of young people's sexual health was carried out using rapid participatory appraisal (RPA). A technique new to participatory needs assessment, meta-planning, was used for the ...appraisal. Presents the evaluation of meta-planning as a technique for RPA in the area of young people's sexual health. (Original abstract - amended)
A health needs assessment of young people's sexual health was carried out using rapid participatoiy appraisal (RPA). A technique new to participatory needs assessment, meta-planning, was used. for ...the appraisal. This paper pre sents the evaluation of meta-planning as a technique for RPA in the area of young people's sexual health. Meta-planning compared favourably with other techniques, focus groups and individual interviews, used in RPA. It was efficient, rapid and feasible for young, people to use. This meant that data could be. collected from young people by their peers. Similarity between areas of need idendned by workers and young people in this appraisal, and between these results and other published literature suggests that the results are valid. It is concluded that meta-planning could be used for rapid participatory appraisal of young people's sexual health.
Microglial cells play important roles in brain injury and repair and are implicated in diseases such as Alzheimer's disease, Creutzfeldt–Jacob disease, multiple sclerosis, the Aids Dementia Complex ...and stroke. Despite their importance in neuropathology, the underlying molecular basis for the activation of microglia after brain injury is not understood. We show, using RT-PCR, in situ hybridisation, immunocytochemistry, and electrophoretic mobility shift assay, that the CCAAT-enhancer binding proteinα (C/EBPα), a sequence specific DNA-binding protein, is induced in microglial cells, but not astrocytes or neurons, after hypoxic–ischemic brain injury. These results suggest that C/EBPα might regulate gene expression and consequentially have a role in the activation and/or proliferation of microglia following brain injury.
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