Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Metab Brain Dis. 2012 Dec;27(4):471-8. doi: 10.1007/s11011-012-9333-7. Epub 2012 Sep 5.
A Ketogenic Diet (KD) mimics the anticonvulsant effects of fasting, which are known to suppress seizures. The purinergic system has been investigated in the matter of epilepsy development, especially the nucleoside adenosine, which has been considered a natural brain anticonvulsant. During epileptic seizures, extracellular adenosine concentration rises rapidly to micromolar levels. Adenosine can exert its anticonvulsant functions, after its release by nucleoside bidirectional transport, or by production through the sequential catabolism of ATP by ectonucleotidases, such as E-NTPDases (ectonucleoside triphosphate diphosphohydrolases) and ecto-5'-nucleotidase. Here, we have investigated the effect of a ketogenic diet on the nucleotide hydrolysis and NTPDases expression in the lithium-pilocarpine (Li-Pilo) model of epilepsy. For the induction of Status Epileticus (SE), 21-day-old female Wistar rats received an i.p. injection of lithium chloride (127 mg/kg) and 18-19 h later an i.p. injection of pilocarpine hydrochloride (60 mg/kg). The control groups received an injection of saline. After induction of SE, the control and Li-Pilo groups received standard or ketogenic diets for 6 weeks. The lithium-pilocarpine exposure affected the ATP (a decrease of between 8 % and 16 %) and ADP (an increase of between 18 % and 22 %) hydrolysis in both groups whereas the diet did not impact the nucleotide hydrolysis. NTPDase2 and 3 mRNA expressions decreased in the Li-Pilo group (41 % and 42 %). This data highlights the participation of the purinergic system in the pathophysiology of this model of epilepsy, since nucleotide hydrolysis and NTPDase expressions were altered by Li-Pilo exposure, with no significant effects of the ketogenic diet. However, the interaction between purinergic signaling and a ketogenic diet on epilepsy still needs to be better elucidated.
生酮饮食（KD）模拟禁食的抗惊厥作用，已知禁食可抑制癫痫发作。嘌呤能系统已在癫痫发展的研究中进行了研究，特别是核苷腺苷，它被认为是一种天然的脑抗惊厥剂。在癫痫发作期间，细胞外腺苷浓度迅速上升至微摩尔水平。腺苷可以发挥其抗惊厥作用，在核苷双向转运后释放，或通过核苷酸酶的顺序分解代谢 ATP 产生，例如 E-NTPDases（核苷酸三磷酸二磷酸水解酶）和外核苷酸酶 5'-核苷酸酶。在这里，我们研究了生酮饮食对锂-匹罗卡品（Li-Pilo）癫痫模型中核苷酸水解和 NTPDases 表达的影响。为了诱导癫痫持续状态（SE），21 天大的雌性 Wistar 大鼠接受腹腔注射氯化锂（127mg/kg），18-19 小时后腹腔注射盐酸匹罗卡品（60mg/kg）。对照组接受生理盐水注射。SE 诱导后，对照组和 Li-Pilo 组分别接受标准饮食或生酮饮食 6 周。锂-匹罗卡品暴露影响了两组的 ATP（降低 8%-16%）和 ADP（升高 18%-22%）水解，而饮食对核苷酸水解没有影响。NTPDase2 和 3 mRNA 表达在 Li-Pilo 组降低（41%和 42%）。该数据突出了嘌呤能系统在该癫痫模型病理生理学中的参与作用，因为核苷酸水解和 NTPDase 表达受 Li-Pilo 暴露的影响，而生酮饮食没有显著影响。然而，嘌呤能信号与生酮饮食对癫痫的相互作用仍需要更好地阐明。
