Dipartimento di Ricerca Traslazionale e Delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, Pisa, Italy.
PLoS One. 2013;8(1):e53605. doi: 10.1371/journal.pone.0053605. Epub 2013 Jan 4.
Acetyl-L-carnitine (ALC) is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.
乙酰左旋肉碱(ALC)是一种天然存在的物质,当以超生理浓度给药时,具有神经保护作用。它参与膜稳定和增强线粒体功能。由于其在各种神经疾病中的临床应用,包括阿尔茨海默病和痛性神经病,该分子引起了相当大的关注。ALC 已知可改善长期用药物治疗的老年动物的认知能力,最近有报道称,它可损害水蛭的非联想学习形式。在本研究中,分析了乙酰左旋肉碱对医用水蛭 Hirudo medicinalis 基因表达的影响。抑制差减杂交方法用于生成差减 cDNA 文库,随后在 ALC 处理后鉴定水蛭神经系统中差异表达的转录本。该方法不仅可以检测差异表达的基因转录本,还可以检测其序列或身份仍未知的基因的转录本。我们报告称,单次给予 ALC 能够积极调节编码功能的基因的表达,这些功能显示出 ALC 对无脊椎动物的持久作用,并证实了该物质的神经保护和神经调节作用。此外,一个重要的发现是植物源性基因的调节。这可能被认为是外共生互惠的一个实例。