Alzheimer’s disease (AD) is a neurodegenerative disorder associated with the accumulation of amyloid ?42 (A?42). Microglia promote the clearance and phagocytosis of A?, suggestive of the neuroprotective roles of microglia in AD. In addition, AD is characterized by an increase in the level of prostaglandins (PGs) in the cerebrospinal fluid, thereby supporting the hypothesis that the inflammatory action of brain PGs may be associated with the preclinical development of AD. Several studies have focused on Hematopoietic-type PGD2 synthase (HPGDS) in various tissues, very little is known about the role of HPGDS in AD. In the present study, we attempted to determine the role of HPGDS in A? clearance by microglia cells. We used in vitro and in vivo mouse models that recapitulate acute and chronic aspects of microglial responses to A? peptides. In this study, we used in vitro and in vivo strategies to reveal that microglial HPGDS activity negatively regulates multiple and distinct beneficial functions that are critical to suppress the harmful effects of accumulating A?42. Together, our findings in distinct mouse models of A? inflammation demonstrated that the deletion of microglial HPGDS restores chemotaxis, A? clearance, regulation of inflammatory responses, and trophic factor generation and signaling.

The north eastern Mediterranean coast of Libya is facing impacts of multiple anthropogenic activities. The present investigation aims to assess the impacts of metal pollutants in their complex state on mullet fish; Mugil cephalus collected from a reference site in comparison to other three sites along this area. Histopathological changes in gill, liver and kidney samples as well as DNA fragmentation and RAPD-PCR analyses showed site-specific patterns in accordance with the detected metal concentrations (Cu, Zn, Mn, Cd, Pb, Fe and Al) in fish vital organs and the metal pollution index (MPI). Generally, the results showed that site 1 (Benghazi City) followed by site 3 (Tobrok City) were the most contaminated areas in comparison to both site 2 (Sousa City) and site 4 (El-burdi City – the reference site). The highest percentage of DNA fragmentation was recorded significantly in site 1 followed by site 3. RAPD-PCR analysis showed high similarity among fish collected from sites 2 and 3, medium similarity among fish collected from both sites 2 and 3 in relation to site 4 and low similarity between fish of site 1 in relation to other sites. The hazard index (HI), as an indicator of human health risks associated with fish consumption, showed safe limits for all studied metals except for Cd in sites 1, 2 and 3 at subsistence skin consumption and in site 1 at subsistence muscle consumption. This does not neglect the fact that the cumulative risk effect for metals together gives an alarming sign and the health of fish consumers is endangered around the studied polluted sites. In conclusion, the continued industrial, agricultural and domestic discharges into the Mediterranean Sea coast of Libya can pose threat to both inhabiting biota and public health. Furthermore, M. cephalus proved to be a suitable sentinel species that can be used in monitoring and assessing the pollution status in marine ecosystems with different pollution gradients. Regular metal assessment surveys and advisories for fish consumption are recommended for water bodies around densely populated areas to alarm the society for the future risk.