Neonatal exposure to the cyanobacterial toxin BMAA induces changes in protein expression and neurodegeneration in adult hippocampus.
Neonatal exposure to the cyanobacterial toxin BMAA induces changes in protein expression and neurodegeneration in adult hippocampus.
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新生儿暴露于蓝细菌毒素BMAA会诱导成年海马蛋白表达和神经退行性的变化。
DOI：
10.1093/toxsci/kfs241
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Andersson M
中科院分区：
文献类型：
--
作者：
Karlsson O;Berg AL;Lindström AK;Hanrieder J;Arnerup G;Roman E;Bergquist J;Lindquist NG;Brittebo EB;Andersson M
蓝藻毒素β-N-甲氨基-L-丙氨酸(BMAA)被认为与神经退行性疾病有关。我们之前已经报道了小鼠新生海马区选择性摄取BMAA，新生期暴露会导致成年大鼠学习和记忆障碍。这项研究的目的是描述用谷氨酸能BMAA治疗6月龄大鼠(出生后9-10天)对大脑的影响。用基质辅助激光解吸电离(MALDI)成像质谱仪(IMS)直接成像脑冷冻切片中蛋白质的变化，并通过免疫组织化学和组织病理学观察组织学变化。结果显示，长期的变化包括成年海马区能量代谢和细胞内信号相关蛋白表达减少，剂量为150 mg/kg时，该脑区没有出现组织病理损害。发育过程中暴露于较高剂量(460 mg/kg)也会导致S100β、组蛋白、钙和钙调蛋白结合蛋白以及鸟嘌呤核苷酸结合蛋白表达的变化。在此剂量下，成人海马区的严重损伤包括神经元变性、细胞丢失、钙沉积和星形胶质细胞增生症。这些数据显示，较低的新生儿剂量的BMAA对成年海马区的影响微妙，有时是剂量依赖的，但却是永久性的，这表明BMAA可能会潜在地干扰发育过程中的许多过程。海产品中BMAA的检测强调了评估人类暴露于这种神经毒素的程度的重要性。
The cyanobacterial toxin β-N-methylamino-l-alanine (BMAA) has been proposed to contribute to neurodegenerative disease. We have previously reported a selective uptake of BMAA in the mouse neonatal hippocampus and that exposure during the neonatal period causes learning and memory impairments in adult rats. The aim of this study was to characterize effects in the brain of 6-month-old rats treated neonatally (postnatal days 9–10) with the glutamatergic BMAA. Protein changes were examined using the novel technique Matrix-Assisted Laser Desorption Ionization (MALDI) imaging mass spectrometry (IMS) for direct imaging of proteins in brain cryosections, and histological changes were examined using immunohistochemistry and histopathology. The results showed long-term changes including a decreased expression of proteins involved in energy metabolism and intracellular signaling in the adult hippocampus at a dose (150mg/kg) that gave no histopathological lesions in this brain region. Developmental exposure to a higher dose (460mg/kg) also induced changes in the expression of S100β, histones, calcium- and calmodulin-binding proteins, and guanine nucleotide-binding proteins. At this dose, severe lesions in the adult hippocampus including neuronal degeneration, cell loss, calcium deposits, and astrogliosis were evident. The data demonstrate subtle, sometimes dose-dependent, but permanent effects of a lower neonatal dose of BMAA in the adult hippocampus suggesting that BMAA could potentially disturb many processes during the development. The detection of BMAA in seafood stresses the importance of evaluating the magnitude of human exposure to this neurotoxin.
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影响因子：
5.3
作者：
Bernal, F;Saura, J;Mahy, N
通讯作者：
Mahy, N
影响因子：
48
作者：
Andersson, Malin;Groseclose, M. Reid;Caprioli, Richard M.
通讯作者：
Caprioli, Richard M.
影响因子：
2.7
作者：
Karlsson, Oskar;Roman, Erika;Brittebo, Eva B.
通讯作者：
Brittebo, Eva B.
影响因子：
4.8
作者：
Gouraud, S. S.;Heesom, K.;Murphy, D.
通讯作者：
Murphy, D.
影响因子：
5.4
作者：
Banack SA;Johnson HE;Cheng R;Cox PA
通讯作者：
Cox PA