Lovastatin improves neurological outcome after nucleus basalis magnocellularis lesion in rats.
Increasing evidence indicates that statins, specific inhibitors of 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase, exerts neuroprotective actions rather than simply lowering cholesterol. However, the underlying mechanism has not been elucidated clearly. Here, the effect of lovastatin on the neurological outcomes of nucleus basalis magnocellularis (NBM)-lesioned rats and the pathophysiological mechanisms were investigated. Sprague-Dawley rats were divided into three groups: (i) a sham group; (ii) a model group: bilateral NBM of rats were injured by infusion of ibotenic acid; and (iii) a lovastatin-treated group: lovastatin was administrated orally for 4 weeks before treated by ibotenic acid. We show that lovastatin significantly improves the neurological outcomes as well as the choline acetyltransferase (ChAT) activity and muscarinic/NMDA receptor binding activity impaired by NBM lesion, and that lovastatin prevents neuron loss and induces Akt whereas inhibits p38 phosphorylation. Overall, the neuro-restorative and -protective effect of lovastatin may be attributed to the regulation of Akt- and p38-mediated signaling pathway together with improvement of muscarinic/NMDA receptor functions. Statins may be useful in the treatment of neurological disorders.
Zhao
Z
Z
College of Traditional Chinese Medicine, Hebei Medical University, Shijiazhuang, PR China.
Zhao
S
S
Xu
N
N
Yu
C
C
Guan
S
S
Liu
X
X
Huang
L
L
Liao
W
W
Jia
W
W
D000109:Acetylcholine / Q000096:biosynthesis / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000378:metabolism / Q000503:physiopathology*; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003714:Denervation; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007051:Ibotenic Acid / Q000633:toxicity; D008148:Lovastatin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009498:Neurotoxins / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009498:Neurotoxins; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D008148:Lovastatin; D002795:Choline O-Acetyltransferase; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D000109:Acetylcholine