RT Journal Article
T1 Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke
A1 Hurtado Moreno, Olivia
A1 Hernández Jiménez, Macarena
A1 Zarruk, Juan G.
A1 Cuartero Desviat, María Isabel
A1 Ballesteros, Iván
A1 Camarero, Guadalupe
A1 Moraga Yébenes, Ana
A1 Pradillo Justo, Jesús Miguel
A1 Moro Sánchez, María Ángeles
A1 Lizasoaín Hernández, Ignacio
AB CDP-choline has shown neuroprotective effects in cerebral ischemia. In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. Several mechanisms have been proposed to explain the beneficial actions of CDP-choline. We have now studied the participation of Sirtuin1 (SIRT1) in the neuroprotective actions of CDP-choline. Fischer rats and Sirt1⁻/⁻ mice were subjected to permanent focal ischemia. CDP-choline (0.2 or 2 g/kg), sirtinol (a SIRT1 inhibitor; 10 mg/kg), and resveratrol (a SIRT1 activator; 2.5 mg/kg) were administered intraperitoneally. Brains were removed 24 and 48 h after ischemia for western blot analysis and infarct volume determination. Treatment with CDP-choline increased SIRT1 protein levels in brain concomitantly to neuroprotection. Treatment with sirtinol blocked the reduction in infarct volume caused by CDP-choline, whereas resveratrol elicited a strong synergistic neuroprotective effect with CDP-choline. CDP-choline failed to reduce infarct volume in Sirt1⁻/⁻ mice. Our present results demonstrate a robust effect of CDP-choline like SIRT1 activator by up-regulating its expression. Our findings suggest that therapeutic strategies to activate SIRT1 may be useful in the treatment of stroke. Sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions. Regarding stroke, there is no direct evidence. We have demonstrated that citicoline increases SIRT1 protein levels in brain concomitantly to neuroprotection. Citicoline fails to reduce infarct volume in Sirt1⁻/⁻ mice. Our findings suggest that therapeutic strategies acting on SIRT1 may be useful in the treatment of stroke.
PB Wiley
SN 0022-3042
SN 1471-4159
YR 2013
FD 2013-05-13
LK https://hdl.handle.net/20.500.14352/96288
UL https://hdl.handle.net/20.500.14352/96288
LA eng
NO Hurtado O, Hernández-Jiménez M, Zarruk JG, Cuartero MI, Ballesteros I, Camarero G, Moraga A, Pradillo JM, Moro MA, Lizasoain I. Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke. J Neurochem. 2013 Sep;126(6):819-26. doi: 10.1111/jnc.12269
DS Docta Complutense
RD 12 abr 2025