The effect of simvastatin treatment on behavioral parameters, cognitive performance, and hippocampal morphology in rats fed a standard or a high-fat diet.
The aim of this study was to examine the effect of simvastatin (SMV), a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, in rats fed with a standard or a high-fat diet (HFD) throughout the prenatal and the postnatal periods. The emotional status of the animals was evaluated by elevated plus-maze and modified forced swimming tests, whereas cognitive performance was assessed by a Morris water maze task. Morphological changes in the hippocampus were examined by design-based stereology. HFD exposure significantly increased blood serum triglycerides without altering cholesterol levels relative to the controls. After four weeks of oral SMV (5 mg/kg) administration, serum triglycerides reverted to the control level. SMV caused significant anxiolytic, antidepressant-like, and nootropic effects in animals fed the standard diet. In the HFD group, enhanced anxiety and depression, and reduced cognitive performances of animals were reversed by SMV treatment. Although a total volume estimation of the hippocampal subfields indicated no significant change among the groups, the total number of pyramidal neurons decreased significantly in animals fed the HFD; following SMV treatment, this detrimental effect was reversed. In conclusion, chronic SMV administration has significant therapeutic potential for the treatment of affective and cognitive disorders with or without altering the serum lipid profiles.
Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey. ozgurdt@anadolu.edu.tr
Özgür Devrim
ÖD
Can
Emel
E
Ulupınar
Ümide Demir
ÜD
Özkay
Bengi
B
Yegin
Yusuf
Y
Öztürk
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000188:drug therapy* / Q000196:embryology / Q000503:physiopathology / Q000517:prevention & control; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000627:therapeutic use; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D019821:Simvastatin