Citicoline protects hippocampal neurons against apoptosis induced by brainbeta-amyloid deposits plus cerebral hypoperfusion in rats

Citicoline is an endogenous intermediate involved in the biosynthesis of br ain phospholipids and acetylcholine which has been extensively used for the treatment of several neurodegenerative conditions. The effects of citicoli ne on neurodegeneration, apoptosis and learning were investigated in male S prague Dawley rats subjected to implants of the beta-amyloid fragment 1-40 (A beta 4; 3 Mmol) into the light hippocampus and to permanent unilateral o cclusion of the carotid artery Citicoline (CDP: 0, 62.5, 125 and 250 mg/kg/ day i.p.) was given during 2 days before and for 5 days after surgery, and the extension of the degeneration and the number of apoptotic figures (TUNE L technique) were evaluated in the dentate gyrus (DG) and the CA1 area of t he the hippocampus. Citicoline, at 125 and 250 mg/kg, reduced the number of apoptotic neurons in the hippocampus of rats mts with A beta 4/hypoper-fus ion-induced neurodegeneration (CDP0 = 105.3 +/- 32.8 apoptotic figures; CDP 125 = 39.2 +/- 7.4** apoptotic figures; CDP250 = 34.5 +/- 14.4** apoptotic figures; **p < 0.01 vs. CDP0). CDP also reduced neuronal degeneration in fi le CA1 area in a dose-dependent manner-(CDP0 = 450.5 +/- 130.1 mu m; CDP62. 5 = 280.6 +/- 76.3 mu m; CDP125 = 86.6 +/- 37.3* mu m; CDP250 = 121.7 +/- 8 5.3* mu m; p < 0.05 vs. CDP0). Variability of results was very high in the DG, where a significant reduction in the extent of neurodegeneration was on ly observed in the group of rats receiving 2.5 mg/kg of citicoline. Finally , citicoline improved retention of a passive avoidance learning task, incre asing th number of avoidances (Av) (CDP0 = 4.2 +/- 0.7 Av; CDP62.5 = 6.9 +/ - 1.0 Av; CDP125 = 7.9 +/- 0.7** Av; CDP250 = 8.5 +/- 0.6** Av; **p < 0.01 vs. CDP0) in a dose-related manner. Based on these results, it was conclude d that citicoline exerts antiapoptotic, neuroprotective and antiamnestic ef fects in conditions of neurodegeneration induced by A beta 4 plus hypoperfu sion. (C)1999 Prous Science. All rights reserved.