Reversible aberration of neurogenesis affecting late-stage differentiation in the hippocampal dentate gyrus of rat offspring after maternal exposure to manganese chloride

Exposure to MnCl2 · 4H2O during development induces activation of microglial and perivascular macrophage populations in the hippocampal dentate gyrus of rats

“…With regard to offspring developmental parameters, no statistically significant differences were observed between each treatment and control groups in the body weight, food consumption, external differentiation with regard to pinna detachment, eruption of lower incisor, opening of eyelid, opening of vagina and cleavage of the balanopreputial gland, and organ weights of offspring after birth through to PND 77 (Ohishi et al ., ).…”

“…The estimated daily intake of Mn per body weight in adults (taken as 50 kg) was within the range of 0.04–0.1 mg kg –1 body weight day –1 . In contrast, the total Mn intake of the dams in the present study was estimated to be 10.34 mg kg –1 body weight day –1 on the 32 ppm Mn diet, 15.10 mg kg –1 body weight day –1 on the 160 ppm Mn diet and, 38.76 mg kg –1 body weight day –1 on the 800 ppm Mn diet (Ohishi et al ., ). Therefore, the total Mn intake by the dams treated with MnCl 2 · 4H 2 O at 800 ppm was approximately 380–970 times greater than the ESADDI in adult humans.…”

“…Therefore, the total Mn intake by the dams treated with MnCl 2 · 4H 2 O at 800 ppm was approximately 380–970 times greater than the ESADDI in adult humans. However, we detected no toxicity in the dams, even at 800 ppm, which is consistent with the lack of changes in the Mn concentrations in the maternal brains (Ohishi et al ., ). In contrast, the offspring showed slight increases in the distribution of the doublecortin (DCX) + granule cell population and the reelin + interneurons in the dentate gyrus of the hippocampus after 800 ppm MnCl 2 · 4H 2 O, and an increase in brain Mn concentration after ≥ 160 ppm MnCl 2 · 4H 2 O (Ohishi et al ., ).…”

Manganese and aging

“…Rats exposed to Mn in utero from gestational day 10 through post-natal day 21 showed an increase in doublecortin positive cells in the subgranular zone, indicating an increase in immature granule cells, as well as an increase in reelin positive cells 72 . Reelin is an extracellular matrix protein necessary for neuronal migration and targeting.…”

Developmental Effects of Manganese

“…Similarly, maternal exposure of pregnant rats to manganese chloride impacts late-stage differentiation in the dentate gyrus of the offspring. 38 DNA methylation patterns, which are tightly coupled to cellular differentiation, 39 were disrupted in the offspring of mice exposed to manganese chloride during pregnancy 40 through aberrant promoter methylation of genes involved in neurogenic development, which include Pvalb and Atp1a3. Interestingly, the observed methylation differences for Pvalb eroded in older pups, while the increases in Atp1a3 promoter methylation were sustained into adulthood.…”