Marschallinger, Julia and Schaeffner, Iris and Klein, Barbara and Gelfert, Renate and Rivera, Francisco J. and Illes, Sebastian and Grassner, Lukas and Janssen, Maximilian and Rotheneichner, Peter and Schmuckermair, Claudia and Coras, Roland and Boccazzi, Marta and Chishty, Mansoor and Lagler, Florian B. and Renic, Marija and Bauer, Hans-Christian and Singewald, Nicolas and Bluemcke, Ingmar and Bogdahn, Ulrich and Couillard-Despres, Sebastien and Lie, D. Chichung and Abbracchio, Maria P. and Aigner, Ludwig (2015) Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug. NATURE COMMUNICATIONS, 6: 8466. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LEUKOTRIENE RECEPTOR-1 ANTAGONIST; SPINAL-CORD-INJURY; HIPPOCAMPAL NEUROGENESIS; ALZHEIMERS-DISEASE; AUTOIMMUNE ENCEPHALOMYELITIS; PROGENITOR PROLIFERATION; MICROGLIAL ACTIVATION; COGNITIVE FUNCTION; CEREBRAL-ISCHEMIA; CELL HOMEOSTASIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Jun 2019 08:05 |
| Last Modified: | 06 Jun 2019 08:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4667 |
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