In the search for ways to combat degenerative neurological disorders, neurogenesis-stimulating factors are proving to be a promising area of research. In this study, we show that the hormonal factor prolactin (PRL) can activate a pool of latent precursor cells in the adult mouse hippocampus. Using an in vitro neurosphere assay, we found that the addition of exogenous PRL to primary adult hippocampal cells resulted in an approximate 50% increase in neurosphere number. In addition, direct infusion of PRL into the adult dentate gyrus also resulted in a significant increase in neurosphere number. Together these data indicate that exogenous PRL can increase hippocampal precursor numbers both in vitro and in vivo. Conversely, PRL null mice showed a significant reduction (approximately 80%) in the number of hippocampal-derived neurospheres. Interestingly, no deficit in precursor proliferation was observed in vivo, indicating that in this situation other niche factors can compensate for a loss in PRL. The PRL loss resulted in learning and memory deficits in the PRL null mice, as indicated by significant deficits in the standard behavioral tests requiring input from the hippocampus. This behavioral deficit was rescued by direct infusion of recombinant PRL into the hippocampus, indicating that a lack of PRL in the adult mouse hippocampus can be correlated with impaired learning and memory.

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Introduction Nonsteroidal anti-inXammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory eVects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531. Materials and methods The eVects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacriWced. Tumor size, immune cell inWltration, caspase-3 activity, PGE 2 and celecoxib levels were determined.Results CC531 tumors did not show COX-2 expression. Tumor growth was signiWcantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell inWltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only signiWcantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 g/ml signiWcantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 g/ml were needed to aVect tumor cell viability. Conclusion These results suggest that the inhibitory eVects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth.

Upon infection with Salmonella, a host develops an immune response to limit bacterial growth and kill and eliminate the pathogen. Salmonella has evolved mechanisms to remain dormant within the body, only to reappear (reactivate) at a later time when the immune system is abated. We have developed an in vivo model for studying reactivation of Salmonella enterica serovar Typhimurium infection in mice. Upon subcutaneous infection, C3H/HeN (Ity r ) mice showed an increase in bacterial numbers in livers and spleens, which reached a peak on day 19. After full recovery from the infection, these mice were irradiated or depleted of CD4 ؉ T cells. The mice displayed a secondary infection peak in livers and spleens with a course similar to that of the primary infection. We concluded that CD4 ؉ T cells are involved in active suppression of S. enterica serovar Typhimurium during latency. The role of CD4 ؉ T cells during primary infection with S. enterica serovar Typhimurium is well established. This is the first study to describe a role of CD4 ؉ T cells during the latent phase of S. enterica serovar Typhimurium infection.