title: Simvastatin is the statin that most efficiently protects against kainate-induced excitotoxicity and memory impairment.
abstract: Statins have recently been shown to act as protectants against several neuropathological conditions. They have received special attention in the field of Alzheimer's disease (AD), where epidemiological studies indicating a lower prevalence of AD/dementia in statin-prescribed populations. Excitotoxicity, which derives from the overstimulation of glutamate receptors, is a major cause of neuron death in several neurological diseases, including AD and epilepsy. We have carried out a comparative study to investigate the effects of all the commercially available statins (simvastatin, lovastatin, fluvastatin, pravastatin, and atorvastatin) on neuron damage and memory impairment. To this end, we studied neurodegeneration in a mouse model by systemic administration of kainate. Simvastatin was the most effective statin in reducing the deleterious effects caused by kainate, including the severity of seizures, excitotoxicity, oxidative damage, neuritic dystrophy and apoptosis in the hippocampus and other limbic structures of the brain cortex. Lovastatin was the second most efficient statin in preventing seizures and histopathological signs of excitotoxicity, whilst fluvastatin, pravastatin, and atorvastatin showed neither antiepileptic nor neuroprotective effects. Only simvastatin enhanced episodic-like memory. To the best of our knowledge this is the first in vivo study to analyze the neuroprotective effect of all the commercially available statins. Our results suggest that both simvastatin and lovastatin (but especially simvastatin) may well have therapeutic potential in the treatment of neurodegenerative diseases involving excitotoxicity and memory impairment, including AD.
authors.affiliation: NEURON BPh, BioPharma Division, Parque Tecnológico de Ciencias de Salud, Edif. BIC-Granada, Armilla, Granada, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ramirez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Tercero
authors.forename: Antonia
authors.initials: A
authors.lastname: Pineda
authors.forename: Javier S
authors.initials: JS
authors.lastname: Burgos
mesh_terms: D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007608:Kainic Acid / Q000633:toxicity*; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018690:Excitatory Amino Acid Agonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D019821:Simvastatin; D007608:Kainic Acid