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Selected PublicationsNeurosciences
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Abstract
Statins are widely being used for the treatment of a variety of conditions beyond their original indication for lowering
cholesterol. We have previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate
locomotor and anxiety effects along with the regional changes of N-methyl-d-aspartate (NMDA) receptors in the rat brain after 4-week
administration of simvastatin. Hyperlocomotive and anxiolytic-like activities in the rat were observed after chronic administration of
high dose simvastatin (10 mg/kg/day). Distributions and alterations of NMDA receptors in the post-mortem rat brain were
detected by [(3)H] MK-801 binding autoradiography. Simvastatin increased [(3)H] MK-801 binding, predominantly in the prefrontal
cortex (20%, p=0.003), primary motor cortex (20%, p<0.001), cingulate cortex (28%, p<0.001),
hippocampus (41%, p<0.001), caudate putamen (30%, p=0.029), nucleus accumbens (27%, p=0.035) and amygdala (45%, p<0.001) compared to controls.
Significant positive correlations were identified between hyperlocomotive as well as anxiolytic-like activities and the upregulation of NMDA
receptors in different brain regions. Our results also provide strong evidence that chronic high dose simvastatin administration is to exhibit
NMDA antagonist-like effects, which would partially explain the anxiolytic and hyperlocomotor activities. These findings contribute to a
better understanding of the critical roles of simvastatin in modulating psycho-neurodegenerative disorders, via NMDA receptors.
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Oncology
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Microbiology
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Technical publications
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