Abstract TMP72: L-carnitine Enhances Axonal Plasticity Via Akt/mammalian Target Of Rapamycin Pathway In A Rat Chronic Cerebral Hypoperfusion
Background and Purpose: Chronic cerebral hypoperfusion (CCH) induces white matter lesions with oligodendrocytic damage and causes cognitive impairment. Oxidative stress has been elucidated as a pivotal role of its pathophysiology. Damage of axon can be also involved in CCH, however, mechanisms that associated with axonal damage under CCH have not been fully studied. In the present study, we analyzed axonal plasticity and damage of oligodendrocytes in a rat CCH model using L-carnitine, antioxidant agent.
Methods: Adult rats subjected to ligation of bilateral common carotid artery (LBCCA), were randomly divided into two groups: vehicle-treated rats; and L-carnitine-treated rats (600mg/kg/day), and were sacrificed at 7, 14, 21 and 28 days after LBCCA (n=7/group). Sham operated rats (n=7) were used as a control group. The Morris water maze was performed to evaluate spatial learning and memory tasks, and immunohistochemical and Western blot analysis were studied.
Results: Rats subjected to LBCCA substantially increased escape latency on the Morris water maze in a time-dependent fashion. L-carnitine-treated rats significantly reduced escape latency compared to vehicle-treated rats at 28 days after LBCCA (P<0.05). Protein levels of phosphorylated neurofilament heavy protein (pNFH), a marker of axons, were reduced after LBCCA, however, L-carnitine significantly increased pNFH levels compared to levels in vehicle-treated rats at 28 days after LBCCA (P<0.01). Concurrently, increases of phosphorylated Akt (P<0.05) and mammalian target of rapamycin (mTOR) (P<0.05) were detected in L-carnitine-treated rats compared to vehicle-treated rats at 28 days after LBCCA. 4-hydroxy-2-nonenal (HNE)+ and 8-hydroxy-deoxyguanosine (8-OHdG)+, markers of oxidative stress, oligodendrocytes substantially increased until 28 days after LBCCA (P<0.001). L-carnitine-treated rats significantly reduced HNE+ and 8-OHdG+ oligodendrocytes at each time point after LBCCA (P<0.001).
Conclusion: Our results indicated that L-carnitine increased axonal plasticity via Akt/mTOR pathway and ameliorated oxidative stress in oligodendorocytes damaged by LBCCA, and thereby resulting an improvement of cognitive impairment in a rat CCH model.
- © 2012 by American Heart Association, Inc.