"In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus). Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n = 26), or women who had Alzheimer’s disease (n = 33). We report that 63% of the females (37 of 59) tested harboured male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p = 0.03) and concentration (p = 0.06) of male microchimerism in the brains of women with Alzheimer’s disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain."
The following is fascinating
"Because AD is more prevalent in women than men and an increased risk has been reported in parous vs. nulliparous women and correlated with younger age of onset [16]–[18], we also investigated male Mc in women with AD. AD is a neurodegenerative disease characterized by elevated levels of amyloid plaques, cerebrovascular amyloidosis, and neurofibrillary tangle [30]. Our results suggesting women with AD have a lower prevalence of male Mc in the brain and lower concentrations in regions most affected by AD were unexpected. However, the number of subjects tested was modest and, as discussed previously, pregnancy history was largely unknown. The explanation for decreased Mc in AD, should this observation be replicated in a larger study, is not obvious. In other diseases, both beneficial and detrimental effects of Mc of fetal origin have been described depending on several factors including the specific type and source of Mc [6]. A significant limitation of the current study was the inability to distinguish the type and source of male Mc, and further studies that distinguish genetically normal from abnormal Mc would be of potential interest.
At present, the biological significance of harboring Mc in the human brain requires further investigation. Mc appears to persist in the blood, bone, and bone marrow for decades [2], [45]and is present among different hematopoietic lineages [46]. Moreover, Mc appears to integrate and generate specific cell types in tissues [10], [11], [47]–[49]. In murine studies, fetal Mc in the maternal brain has been observed to resemble perivascular macrophages, neurons, astrocytes, and oligodendrocytes both morphologically and phenotypically and occupy the respective niches [15], [36]. Thus, it is possible that Mc in the brain is able to differentiate into various mature phenotypes or undergoes fusion with pre-existing cells and acquires a new phenotype, as suggested by murine and human studies in which bone marrow-derived cells circulated to the brain and generated neuronal cells by differentiation, or fused with pre-existing neurons [50]–[53]. Lastly, a few studies have reported an association between parity and decreased risk of brain cancer, raising the possibility that Mc could contribute to immunosurveillance against tumorigenic cells as has been suggested for some other types of malignancy [6], [54]–[56]."
Aucun commentaire:
Enregistrer un commentaire