Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, 90619-900, Brazil.
National Institute of Science and Technology for Translational Medicine (INCT-TM), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasília, Brazil.
Transl Psychiatry. 2018 Sep 3;8(1):176. doi: 10.1038/s41398-018-0232-5.
Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats. In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction. Cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, was examined as a potential drug to reverse iron-induced effects on the parameters analyzed. Male rats received vehicle or iron carbonyl (30 mg/kg) from the 12th to the 14th postnatal days and were treated with vehicle or CBD (10 mg/kg) for 14 days in adulthood. Iron increased Caspase 9, Cytochrome c, APAF1, Caspase 3 and cleaved PARP, without affecting cleaved Caspase 8 levels. CBD reversed iron-induced effects, recovering apoptotic proteins Caspase 9, APAF1, Caspase 3 and cleaved PARP to the levels found in controls. These results suggest that iron can trigger cell death pathways by inducing intrinsic apoptotic proteins. The reversal of iron-induced effects by CBD indicates that it has neuroprotective potential through its anti-apoptotic action.
铁在大脑中的积累已被认为是正常衰老和神经退行性疾病的共同特征。认知功能障碍与人类大脑区域的铁过量有关。我们之前描述过，铁过载会导致严重的记忆缺陷，包括成年大鼠的空间、识别和情感记忆障碍。在本研究中，我们研究了新生期铁过载对参与细胞凋亡途径的蛋白质的影响，如 Caspase 8、Caspase 9、Caspase 3、细胞色素 c、APAF1 和 PARP，试图确定铁过载对导致记忆功能障碍的神经系统细胞死亡的因果作用。大麻素（Cannabidiol，CBD）是大麻的主要非精神活性成分，被认为是一种潜在的药物，可以逆转铁对所分析参数的诱导作用。雄性大鼠在出生后的第 12 至 14 天接受载体或羰基铁（30mg/kg），并在成年期接受载体或 CBD（10mg/kg）治疗 14 天。铁增加了 Caspase 9、细胞色素 c、APAF1、Caspase 3 和裂解的 PARP，但不影响裂解的 Caspase 8 水平。CBD 逆转了铁诱导的作用，使 Caspase 9、APAF1、Caspase 3 和裂解的 PARP 恢复到对照中发现的水平。这些结果表明，铁可以通过诱导内在凋亡蛋白触发细胞死亡途径。CBD 逆转铁诱导作用表明，它通过其抗凋亡作用具有神经保护潜力。
