التفاصيل البيبلوغرافية
| العنوان: |
Acute Inhibition of 11β-Hydroxysteroid Dehydrogenase Type-1 Improves Memory in Rodent Models of Cognition. |
| المؤلفون: |
Mohler, Eric G., Browman, Kaitlin E., Roderwald, Victoria A., Cronin, Elizabeth A., Markosyan, Stella, Bitner, R. Scott, Strakhova, Marina I., Drescher, Karla U., Hornberger, Wilfried, Rohde, Jeffrey J., Brune, Michael E., Jacobson, Peer B., Rueter, Lynne E. |
| المصدر: |
Journal of Neuroscience; 4/6/2011, Vol. 31 Issue 14, p5406-5413, 8p |
| مصطلحات موضوعية: |
DEHYDROGENASES, ANIMAL models of cognition disorders, LABORATORY rodents, ALZHEIMER'S disease, MICRODIALYSIS, SHORT-term memory |
| مستخلص: |
Mounting evidence suggests excessive glucocorticoid activity may contribute to Alzheimer's disease (AD) and age-associated memory impairment. 11β-hydroxysteroid dehydrogenase type-1 (HSD1) regulates conversion of glucocorticoids from inactive to active forms. HSD1 knock-out mice have improved cognition, and the nonselective inhibitor carbenoxolone improved verbal memory in elderly men. Together, these data suggest that HSD1 inhibition may be a potential therapy for cognitive deficits, such as those associated with AD. To investigate this, we characterized two novel and selectiveHSD1inhibitors, A-918446 and A-801195. Learning,memoryconsolidation, and recall were evaluated in mouse 24 h inhibitory avoidance. Inhibition of brain cortisol production and phosphorylation of cAMP response element-binding protein (CREB), a transcription factor involved in cognition, were also examined. Rats were tested in a short-term memory model, social recognition, and in a separate group cortical and hippocampal acetylcholine release was measured via in vivo microdialysis. Acute treatment with A-801195 (10 -30 mg/kg) or A-918446 (3-30 mg/kg) inhibited cortisol production in the ex vivo assay by∼35-90%. Acute treatment with A-918446 improved memory consolidation and recall in inhibitory avoidance and increased CREB phosphorylation in the cingulate cortex. Acute treatment with A-801195 significantly improved short-term memory in rat social recognition that was not likely due to alterations of the cholinergic system, as acetylcholine release was not increased in a separate set of rats. These studies suggest that selective HSD1 inhibitors work through a novel, noncholinergic mechanism to facilitate cognitive processing. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
