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Citicoline ( CDP ‐choline) increases S irtuin1 expression concomitant to neuroprotection in experimental stroke
Author(s) -
Hurtado Olivia,
HernándezJiménez Macarena,
Zarruk Juan G.,
Cuartero María I.,
Ballesteros Iván,
Camarero Guadalupe,
Moraga Ana,
Pradillo Jesús M.,
Moro María A.,
Lizasoain Ignacio
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12269
Subject(s) - neuroprotection , citicoline , choline , pharmacology , resveratrol , medicine , ischemia , sirtuin 1 , stroke (engine) , chemistry , biochemistry , endocrinology , downregulation and upregulation , mechanical engineering , engineering , gene
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 ( SIRT 1) 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 SIRT 1 inhibitor; 10 mg/kg), and resveratrol (a SIRT 1 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 SIRT 1 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 SIRT 1 activator by up‐regulating its expression. Our findings suggest that therapeutic strategies to activate SIRT 1 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.