Neurobiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), 3318, Italia Av., 11600, Montevideo, Uruguay.
Neurobiología Celular y Molecular, Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Mol Neurobiol. 2022 Jun;59(6):3738-3754. doi: 10.1007/s12035-022-02798-3. Epub 2022 Apr 6.
Iron deficiency anemia is a prevalent health problem among pregnant women and infants, particularly in the developing countries that causes brain development deficits and poor cognitive outcomes. Since tissue iron depletion may impair myelination and trigger cellular hypoxic signaling affecting blood vessels, we studied myelination and the neurovascular unit (NVU) in infant rats born to mothers fed with an iron deficient (ID) or control diet from embryonic day 5 till weaning. Blood samples and brains of rat pups at postnatal day (PND) 14 and 30 were analyzed. PND 14 ID rats had severe microcytic hypochromic anemia that was almost reversed at PND 30 although hypomyelination and astrocyte immature phenotype in the corpus callosum were significant at that age. In CA1 hippocampal region, PND 14 and PND 30 ID rats showed significant reduced expression of the receptor β of the platelet-derived growth factor localized in pericytes and associated to aquaporin 4 (AQP4) immunopositive capillaries. Shorter AQP4 + capillaries and reduced AQP4 expression were also evidenced in PND 14 and PND 30 ID rats. In addition, pericyte membrane permeability through large-pore channels was transiently increased in ID rats at PND 14 but not at PND 30, while the blood-brain barrier permeability was not affected. Remarkably, transient increased pericyte permeability found in PND 14 ID rats was not directly related to iron depletion, suggesting the involvement of other iron deficiency anemia-induced mechanisms. In summary, severe ID during gestation and lactation produces persistent hypomyelination and significantly affects hippocampal pericytes and astrocytes in the NVU which may trigger impaired neurovascular function.
缺铁性贫血是孕妇和婴儿中普遍存在的健康问题，尤其是在发展中国家，它会导致大脑发育缺陷和认知能力下降。由于组织缺铁可能会损害髓鞘形成并触发影响血管的细胞缺氧信号，我们研究了从胚胎第 5 天到断奶期，以缺铁（ID）或对照饮食喂养的母亲所生婴儿大鼠的髓鞘形成和神经血管单元（NVU）。分析了出生后第 14 天和第 30 天的大鼠幼仔的血液样本和大脑。尽管 ID 大鼠在出生后第 30 天的大脑皮质白质中的少突胶质细胞发育不全和星形胶质细胞未成熟表型几乎得到逆转，但 ID 大鼠在出生后第 14 天已经出现严重的小细胞低色素性贫血。在 CA1 海马区，出生后第 14 天和第 30 天的 ID 大鼠表现出血小板衍生生长因子受体β的表达显著减少，该受体定位于周细胞并与水通道蛋白 4（AQP4）免疫阳性毛细血管相关。在 ID 大鼠中还证实了出生后第 14 天和第 30 天的 AQP4+毛细血管缩短和 AQP4 表达减少。此外，ID 大鼠在出生后第 14 天的周细胞膜通透性通过大孔通道短暂增加，但在出生后第 30 天没有增加，而血脑屏障通透性不受影响。值得注意的是，在出生后第 14 天的 ID 大鼠中发现的周细胞通透性短暂增加与缺铁无关，这表明涉及其他缺铁性贫血诱导的机制。总之，妊娠和哺乳期严重缺铁会导致持续的少突胶质细胞发育不全，并显著影响 NVU 中的海马周细胞和星形胶质细胞，这可能会导致神经血管功能受损。
