title: Rosiglitazone enhances learning, place cell activity, and synaptic plasticity in middle-aged rats.
abstract: As an antidiabetic agent, rosiglitazone (ROSI) binds and activates peroxisome proliferator-activator receptor gamma (PPARγ), altering the expression of genes involved in glucose uptake and disposal, ultimately affecting glucose regulation. ROSI might therefore be a potential treatment to ameliorate age-related decline in cognitive function, particularly on an insulin-resistant background, where improvements in peripheral insulin sensitivity and central nervous system (CNS) glucose utilization may facilitate recovery of cognitive function. We therefore examined the amelioration potential of ROSI for neurocognitive deficits resulting from aging in an animal model. Behaviorally, acute and chronic ROSI treatments enhanced acquisition of learning in the water plus maze, a modified version of the Morris water maze task. In parallel, restoration of synaptic plasticity in the dentate gyrus of ROSI-treated middle-aged rats was evident after a single dose intake. Additionally, the spatial receptive fields of hippocampal CA1 place cells were significantly improved by chronic ROSI administration. ROSI treatment reversed basal plasma insulin abnormalities and increased hippocampal glucose transporter (GLUT)-3 expression in middle-aged rats. Taken together, these results suggest that ROSI modulates hippocampal circuitry effectively to promote an improvement in cognitive function, possibly via a glucose transporter-3 mechanism.
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
authors.forename: Boon Wan
authors.initials: BW
authors.lastname: Wang
authors.forename: Vincent
authors.initials: V
authors.lastname: Hok
authors.forename: Andrea
authors.initials: A
authors.lastname: Della-Chiesa
authors.forename: Charlotte
authors.initials: C
authors.lastname: Callaghan
authors.forename: Sally
authors.initials: S
authors.lastname: Barlow
authors.forename: Marian
authors.initials: M
authors.lastname: Tsanov
authors.forename: Ranya
authors.initials: R
authors.lastname: Bechara
authors.forename: Elaine
authors.initials: E
authors.lastname: Irving
authors.forename: David J
authors.initials: DJ
authors.lastname: Virley
authors.forename: Neil
authors.initials: N
authors.lastname: Upton
authors.forename: Shane M
authors.initials: SM
authors.lastname: O'Mara
mesh_terms: D000375:Aging / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D004558:Electric Stimulation; D004797:Enzyme-Linked Immunosorbent Assay; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D051274:Glucose Transporter Type 3; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone