A Cheshire | PubMed Health

PubMed1999

Neuroautoantibody immunoreactivity in relation to aging and stress in apolipoprotein E-deficient mice.

Progressive disruption of both the neuroendocrine and immune systems has been correlated with age-associated pathogenesis in patients with Alzheimer's disease and in mice lacking apolipoprotein E (ApoE). In this study, we examined neuroautoimmune and neuroendocrine activities in relation to aging and stress in ApoE-deficient mice. An elevated level of autoantibodies against brain antigens was found in sera from ApoE-deficient mice compared to that of wild-type mice as early as 7-8 weeks of age. However, there was no significant difference between the two genotypes at this age in the effect of stress on serum corticosterone or autoantibody titers. Higher titers of autoantibodies were observed in approximately 12-week-old ApoE-deficient mice, especially in those exposed to chronic stress. Based on Western analysis, sera from ApoE-deficient mice showed a strong immunoreactivity with approximately 78 kDa and approximately 40 kDa brain abundant polypeptides, approximately 58 kDa non-brain tissue abundant antigen, and others of approximately, 80-82 kDa in both the brain and non-brain tissues. Immunofluorescence confocal microscopy showed that the major cellular components recognized by the autoimmune sera from ApoE-deficient mice were associated with neuronal cell nuclei and fiber-like structures in different regions of the brain, including the frontal cortex, lateral cortex and hippocampus. These results suggest that neuroautoimmunity associated with the aging process and exposure to chronic stress may be involved in early development of neurodegeneration in mice with ApoE-deficiency.

Aging↗

PubMed1989

Mitosis in Drosophila development.

Many aspects of the mitotic cycle can take place independently in syncytial Drosophila embryos. Embryos from females homozygous for the mutation gnu undergo rounds of DNA synthesis without nuclear division to produce giant nuclei, and at the same time show many cycles of centrosome replication (Freeman et al. 1986). S phase can be inhibited in wild-type Drosophila embryos by injecting aphidicolin, in which case not only do centrosomes replicate, but chromosomes continue to condense and decondense, the nuclear envelope undergoes cycles of breakdown and reformation, and cycles of budding activity continue at the cortex of the embryo (Raff and Glover, 1988). If aphidicolin is injected when nuclei are in the interior of the embryo, centrosomes dissociate from the nuclei and can migrate to the cortex. Pole cells without nuclei then form around those centrosomes that reach the posterior pole (Raff and Glover, 1989); the centrosomes presumably must interact with polar granules, the maternally-provided determinants for pole cell formation. The pole cells form the germ-line of the developing organism, and as such may have specific requirements for mitotic cell division. This is suggested by our finding that a specific class of cyclin mRNAs, the products of the cyclin B gene, accumulate in pole cells during embryogenesis (Whitfield et al. 1989). Other genes that are essential for mitosis in early embryogenesis and in later development are discussed.

Animals↗