Vorhees Charles V, Graham Devon L, Amos-Kroohs Robyn M, Braun Amanda A, Grace Curtis E, Schaefer Tori L, Skelton Matthew R, Erikson Keith M, Aschner Michael, Williams Michael T
Department of Pediatrics, Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Department of Nutrition, University of North Carolina, Greensboro, NC, USA.
Toxicol Rep. 2014;1:1046-1061. doi: 10.1016/j.toxrep.2014.10.004.
Developmental exposure to manganese (Mn) or stress can each be detrimental to brain development. Here, Sprague-Dawley rats were exposed to two housing conditions and Mn from postnatal day (P)4-28. Within each litter two males and 2 females were assigned to the following groups: 0 (vehicle), 50, or 100 mg/kg Mn by oral gavage every other day. Half the litters were reared in cages with standard bedding and half with no bedding. One pair/group in each litter had an acute shallow water stressor before tissue collection (i.e., standing in shallow water). Separate litters were assessed at P11, 19, or 29. Mn-treated rats raised in standard cages showed no change in baseline corticosterone but following acute stress increased more than controls on P19; no Mn effects were seen on P11 or P29. Mn increased neostriatal dopamine in females at P19 and norepinephrine at P11 and P29. Mn increased hippocampal dopamine at P11 and P29 and 5-HT at P29 regardless of housing or sex. Mn had no effect on hypothalamic dopamine, but increased norepinephrine in males at P29 and 5-HT in males at all ages irrespective of rearing condition. Barren reared rats showed no or opposite effects of Mn, i.e., barren rearing + Mn attenuated corticosterone increases to acute stress. Barren rearing also altered the Mn-induced changes in dopamine and norepinephrine in the neostriatum, but not in the hippocampus. Barren rearing caused a Mn-associated increase in hypothalamic dopamine at P19 and P29 not seen in standard reared Mn-treated groups. Developmental Mn alters monoamines and corticosterone as a function of age, stress (acute and chronic), and sex.
发育过程中接触锰（Mn）或应激各自都可能对大脑发育有害。在此，将斯普拉格-道利大鼠从出生后第（P）4天至28天暴露于两种饲养条件和锰环境中。在每窝中，将两只雄性和两只雌性分配到以下组：0（溶剂对照）、50或100mg/kg锰，每隔一天经口灌胃。每窝中有一半饲养在铺有标准垫料的笼子里，另一半饲养在无垫料的笼子里。每组中的一对在组织采集前（即站在浅水中）经历急性浅水应激源。在P11、19或29天对不同窝的大鼠进行评估。在标准笼子中饲养的经锰处理的大鼠基线皮质酮没有变化，但在急性应激后，P19天时比对照组增加得更多；在P11或P29天时未观察到锰的影响。锰使雌性大鼠在P19天时新纹状体多巴胺增加，在P11和P29天时去甲肾上腺素增加。无论饲养条件或性别如何，锰使大鼠在P11和P29天时海马多巴胺增加，在P29天时5-羟色胺增加。锰对下丘脑多巴胺没有影响，但在P29天时使雄性大鼠去甲肾上腺素增加，并且在所有年龄段使雄性大鼠5-羟色胺增加，与饲养条件无关。在无垫料环境中饲养的大鼠对锰没有反应或有相反的反应，即无垫料饲养 + 锰减弱了急性应激引起的皮质酮增加。无垫料饲养也改变了锰诱导的新纹状体中多巴胺和去甲肾上腺素的变化，但未改变海马中的变化。无垫料饲养导致在P19和P29天时下丘脑多巴胺与锰相关的增加，这在标准饲养的经锰处理组中未观察到。发育过程中的锰暴露会根据年龄、应激（急性和慢性）以及性别改变单胺类物质和皮质酮。
Zotero 插件
