title: GluN2B N-methyl-D-aspartic acid receptor subunit mediates atorvastatin-Induced neuroprotection after focal cerebral ischemia.
abstract: Statins are potent cholesterol biosynthesis inhibitors that exert protective effects in humans and in experimental models of stroke. The mechanisms involved in these protective actions are not completely understood. This study evaluates whether atorvastatin (ATV) treatment affects the GluN1 and GluN2B subunits of the N-methyl-D-aspartic acid receptor in the somatosensory cerebral cortex at short and long periods following ischemia. Sham and ischemic male Wistar rats received 10 mg/kg of ATV or placebo by gavage every 24 hr for 3 consecutive days. The first dose was administered 6 hr after ischemia-reperfusion or the sham operation. ATV treatment resulted in faster recovery of neurological scores than placebo, prevented the appearance of pyknotic neurons, and restored microtubule-associated protein 2 and neuronal nuclei staining to control values in the somatosensory cerebral cortex and the hippocampus at 72 hr and 15 days postischemia. Furthermore, ATV prevented spatial learning and memory deficits caused by cerebral ischemia. Cerebral ischemia reduced the number of GluN1/PSD-95 and GluN2B/PSD-95 colocalization clusters in cortical pyramidal neurons and reduced the levels of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. These effects of the ischemic insult were prevented by ATV, which also induced GluN2B/PSD-95 colocalization in neuronal processes and an association of GluN2B with TrkB. The GluN2B pharmacological inhibitor ifenprodil prevented the increase in BDNF levels and the motor and cognitive function recovery caused by ATV in ischemic rats. These findings indicate that GluN2B is involved in the neuroprotective mechanism elicited by ATV to promote motor and cognitive recovery after focal cerebral ischemia.
authors.affiliation: Cellular and Molecular Neurobiology Area, Group of Neuroscience of Antioquia, Faculty of Medicine, SIU, University of Antioquia, Medellín, Colombia.
authors.forename: Johanna Andrea
authors.initials: JA
authors.lastname: Gutierrez-Vargas
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Muñoz-Manco
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Gloria Patricia
authors.initials: GP
authors.lastname: Cardona-Gómez
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects; D013003:Somatosensory Cortex / Q000187:drug effects; D013997:Time Factors
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D016194:Receptors, N-Methyl-D-Aspartate; D000069059:Atorvastatin; C010739:ifenprodil
keywords: BDNF; atorvastatin; cerebral ischemia, GluN2B; neuroprotection; synaptic plasticity