Peres Tanara V, Ong Lin K, Costa Ana Paula, Eyng Helena, Venske Débora K R, Colle Dirleise, Gonçalves Filipe M, Lopes Mark W, Farina Marcelo, Aschner Michael, Dickson Phillip W, Dunkley Peter R, Leal Rodrigo B
Programa de Pós-graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, University of Newcastle, NSW, Australia.
Metallomics. 2016 Jun 1;8(6):597-604. doi: 10.1039/c5mt00265f.
Manganese (Mn) is an essential trace element required for a range of physiological processes, but Mn can also be neurotoxic especially during development. Excess levels of Mn accumulate preferentially in the striatum and can induce a syndrome called manganism, characterized by an initial stage of psychiatric disorder followed by motor impairment. In the present study, we investigated the effects of Mn exposure on the developing dopaminergic system, specifically tyrosine hydroxylase (TH) protein and phosphorylation levels in the striatum of rats. Neonatal rats were exposed to Mn intraperitoneally (ip) from post-natal day 8 up to day 12 (PND8-12). Striatal tissue was analysed on PND14 or PND70, to detect either short-term or long-term effects induced by Mn exposure. There was a dose dependent increase in TH protein levels in the striatum at PND14, reaching significance at 20 mg kg(-1) Mn, and this correlated with an increase in TH phosphorylation at serines 40, 31 and 19. However, in the striatum at PND70, a time by which Mn levels were no longer elevated, there was a dose dependent decrease in TH protein levels, reaching significance at 20 mg kg(-1) Mn, and this correlated with TH phosphorylation at Ser40 and Ser19. There was however a significant increase in phosphorylation of TH at serine 31 at 20 mg kg(-1) Mn, which did not correlate with TH protein levels. Taken together our findings suggest that neonatal Mn exposure can have both short-term and long-term effects on the regulation of TH in the striatal dopaminergic system.
锰（Mn）是一系列生理过程所需的必需微量元素，但锰也可能具有神经毒性，尤其是在发育过程中。过量的锰优先在纹状体中积累，并可诱发一种称为锰中毒的综合征，其特征是初期精神障碍，随后出现运动障碍。在本研究中，我们调查了锰暴露对发育中的多巴胺能系统的影响，特别是对大鼠纹状体中酪氨酸羟化酶（TH）蛋白和磷酸化水平的影响。新生大鼠从出生后第8天至第12天（PND8 - 12）经腹腔注射（ip）给予锰。在PND14或PND70分析纹状体组织，以检测锰暴露引起的短期或长期影响。在PND14时，纹状体中TH蛋白水平呈剂量依赖性增加，在锰剂量为20 mg kg(-1)时达到显著水平，这与丝氨酸40、31和19处TH磷酸化增加相关。然而，在PND70时，此时锰水平不再升高，纹状体中TH蛋白水平呈剂量依赖性降低，在锰剂量为20 mg kg(-1)时达到显著水平，这与Ser40和Ser19处TH磷酸化相关。然而，在锰剂量为20 mg kg(-1)时，丝氨酸31处TH磷酸化显著增加，这与TH蛋白水平无关。综合我们的研究结果表明，新生期锰暴露可对纹状体多巴胺能系统中TH的调节产生短期和长期影响。
