Kumar S
Department of Pharmacology and Environmental Toxicology, Dr ALM Post Graduate Institute of Basic Medical Sciences, Taramani, University of Madras, India 600113.
Food Chem Toxicol. 2002 Dec;40(12):1875-80. doi: 10.1016/s0278-6915(02)00180-1.
Aluminium exposure, apart from producing cholinotoxicity, can include changes in other neurotransmitter levels since neurotransmitter levels are closely interrelated. Reports of aluminium (Al) effects on brain neurotransmitters are limited. To investigate the effect of Al on the rat brain serotonergic system, the present study was conducted to explore brain region-specific changes and duration-specific changes. Male Wistar albino rats were exposed orally to Al chloride (AlCl(3).6H(2)O; 320 mg/kg body weight) daily for up to 60 days and changes in the 5-hydroxytrytamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) levels were observed after 4, 14 and 60 days of exposure in olfactory lobe (OLB), cerebellum (CBL), pons (PON), medulla oblongata (MOB), spinal cord (SPI), hypothalamus (HYP), hippocampus (HIP), striatum (STR), midbrain (MBR) and cortex (COR) brain regions. Significantly increased 5-HT levels observed in brain regions OLB (60 days), HIP (4,14 days), STR (14 days), HYP (14, 60 days), MBR (4 and 14 days), PON (4 days), MOB (4 days) and SPI (4, 14 and 60 days) following Al exposure may be due to Al deactivating 5-HT system by decreased release and subsequent breakdown of 5-HT. Decreased 5-HT levels observed in cerebral COR, HIP (60 days) and in CBL after 4 and 60 days of exposure suggest an inhibitory effect of Al on the 5-HT system due to withdrawal of cholinergic input in these brain regions. 5-HIAA level changes correlate with 5-HT level changes in many brain regions studied. The results reveal that the neurochemical changes due to Al were dependent on the duration of exposure and are brain-region-specific. The observed changes may be related to the cholinergic toxicity of Al.
铝暴露除了会产生胆碱毒性外,还可能导致其他神经递质水平的变化,因为神经递质水平之间密切相关。关于铝(Al)对脑内神经递质影响的报道有限。为了研究铝对大鼠脑血清素能系统的影响,本研究旨在探索脑区特异性变化和时间特异性变化。雄性Wistar白化大鼠每天经口给予氯化铝(AlCl₃·6H₂O;320mg/kg体重),持续60天,在暴露4天、14天和60天后,观察嗅叶(OLB)、小脑(CBL)、脑桥(PON)、延髓(MOB)、脊髓(SPI)、下丘脑(HYP)、海马体(HIP)、纹状体(STR)、中脑(MBR)和皮质(COR)等脑区中5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5-HIAA)水平的变化。铝暴露后,在OLB(60天)、HIP(4天、14天)、STR(14天)、HYP(14天、60天)、MBR(4天和14天)、PON(4天)、MOB(4天)和SPI(4天、14天和60天)等脑区观察到5-HT水平显著升高,这可能是由于铝通过减少5-HT的释放和随后的分解来使5-HT系统失活。在暴露4天和60天后,在大脑COR、HIP(60天)和CBL中观察到5-HT水平降低,这表明铝对5-HT系统有抑制作用,原因是这些脑区胆碱能输入的撤回。在许多研究的脑区中,5-HIAA水平变化与5-HT水平变化相关。结果表明,铝引起的神经化学变化取决于暴露时间,且具有脑区特异性。观察到的变化可能与铝的胆碱能毒性有关。