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Many neurodegenerative diseases are characterized by deposits of ubiquitinated and aberrant proteins, suggesting a failure of the ubiquitin–proteasome system (UPS). The aberrant ubiquitin UBB+1 is one of the ubiquitinated proteins accumulating in tauopathies such as Alzheimer's disease (AD) and polyglutamine diseases such as Huntington's disease. We have generated UBB+1 transgenic mouse lines with post-natal neuronal expression of UBB+1, resulting in increased levels of ubiquitinated proteins in the cortex. Moreover, by proteomic analysis, we identified expression changes in proteins involved in energy metabolism or organization of the cytoskeleton. These changes show a striking resemblance to the proteomic profiles of both AD brain and several AD mouse models. Moreover, UBB+1 transgenic mice show a deficit in contextual memory in both water maze and fear conditioning paradigms. Although UBB+1 partially inhibits the UPS in the cortex, these mice do not have an overt neurological phenotype. These mouse models do not replicate the full spectrum of AD-related changes, yet provide a tool to understand how the UPS is involved in AD pathological changes and in memory formation.

The concerted action of many neuropeptides has been implicated in the nervous control of specific behaviors in many molluscs. In the present study, the presence of amidated tetrapeptide Ala-Pro-Gly-Trp-NH2 (APGWamide) in those lobes that are involved in the control of reproductive behavior in Octopus vulgaris has been investigated. APGWamide immunoreactivity was mainly confined to the posterior olfactory lobule and in the inferior frontal system. These areas are involved in Octopus in the processing of either chemotactile sense or olfaction. From these lobes, immunoreactive fibers reached other lobes of the central nervous system (CNS) which could be indirectly involved in the reproductive behavior. APGWamide immunoreactivity was also present in the glandular cells of the oviducal gland in the female reproductive system. These results constitute the first detailed immunolocalization of APGWamide in cephalopods and open a new insight into the possible effects that both distant and close chemical stimuli can exert on neuropeptidergic circuitries, which may affect the reproductive behavior of cephalopods.

Galactogen synthesis in the albumen gland of the slug Limax maximus is under direct endocrine control [J. van Minnen, J. Wijdenes, and P. G. Sokolove (1983) Gen. Comp. Endocrinol. 49, 307-314]. The present results show that dorsal body cells (DBC) present throughout the connective tissue around the circumesophageal brain are the major cellular source of a galactogen synthesis-stimulating factor (GAL-SF). The amount of GAL-SF varies during sexual maturation of L. maximus (a protandrous hermaphrodite): it is low when animals are immature and reaches a peak in the late female phase when the animals prepare to lay eggs. The morphology of DBC also changes during maturation. DBC are small and release little secretory product in immature and early male-phase animals; release is higher and DBC are larger in late female-phase animals. Gel filtration of homogenates of cerebral ganglia on Sephadex G75 yields one peak of GAL-SF activity with an estimated Mr of 4000-7000 Da. Subsequent anion exchange chromatography showed that GAL-SF could be eluted with a linear NaCl gradient; GAL-SF was found in fractions with a NaCl concentration between 0.04 and 0.07 M.