Microglia are derived from hematopoietic stem cells in bone marrow. Some of these stem cells differentiate as monocytes and further differentiate as microglia in the brain (Ritter et al., 2006). Pb is sequestered in bone marrow. Studies are needed to examine whether Pb in bone marrow disrupts critical replenishment of the hematopoietic daughter cell pool, thus reducing the migration of adequate progenitor cell numbers to the brain. Finally, reduced numbers of IBA-1 labeled microglia may suggest that early chronic Pb exposure resulted in direct destruction of microglia. Astrocytes are

typically noted to be the brain’s “lead-sink.” The primary role of microglia however is to scavenge the Androgen Receptor antagonist brain for debris; further studies are needed to examine whether Selleckchem Androgen Receptor Antagonist microglia are destroyed by scavenged Pb particles. Very recent studies have illuminated the critical role of microglia in

brain development (Paolicelli et al., 2011). Additional studies are needed to examine whether pruning abnormalities are evident in mice with early chronic Pb exposure, and whether reduced numbers of functional microglia in lead exposed animals compromises the neuroimmune response system. Given the potential neurodegenerative effects of disrupted neuroimmune function, we also examined DG volume. As compared with controls, DG volume in both exposure groups was significantly decreased, and exposure groups did not differ significantly. Because both exposure groups received chronic dosing, the lack of difference between low and higher exposure groups with regard to DG volume suggested that the chronicity of exposure may have had more neuropathological significance than the amount of Pb to which the mice were exposed. Studies are needed to compare DG volume differences in cases of chronic versus acute exposure, to test how chronicity of

exposure influences the effects of early chronic Pb exposure on brain structure volume. Reduced DG volume could suggest either developmental delay of structure volume, or tissue deterioration in Pb-exposed animals. The lack of difference between low and higher Pb exposure groups suggested that whatever qualitative differences may exist between early chronic Pb exposure levels, Nintedanib (BIBF 1120) delay and/or deteriorative effects on development of dentate gyrus volume are not distinguishable in animals with low and higher exposures. We also examined the association between microglia number and DG volume, and regression analysis suggested that microglia number accounted for only a small amount of variation in DG volume, thus the volumetric differences are likely attributable to other sources, for example, disrupted integrity and/or numbers of other types of glia and/or neurons. Astrocytes are functionally linked to microglia (Section 1) and are far more abundant than microglia.