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Adenosine A2A receptor involves in neuroinflammation-mediated cognitive decline through activating microglia under acute hypobaric hypoxia.
- Source :
-
Behavioural Brain Research . Jul2018, Vol. 347, p99-107. 9p. - Publication Year :
- 2018
-
Abstract
- Hypobaric hypoxia (HH) at high altitudes leads to a wide range of cognitive impairments which can handicap human normal activities and performances. However, the underlying mechanism is still unclear. Adenosine A 2A receptors (A 2A Rs) of the brain are pivotal to synaptic plasticity and cognition. Besides, insult-induced up-regulation of A 2A R regulates neuroinflammation and therefore induces brain damages in various neuropathological processes. The present study was designed to determine whether A 2A R-mediate neuroinflammation involves in cognitive impairments under acute HH. A 2A R knock-out and wild-type male mice were exposed to a simulated altitude of 8000 m for 7 consecutive days in a hypobaric chamber and simultaneously received behavioral tests including Morris water maze test and open filed test. A 2A R expression, the activation of microglia and the production of TNF-α were evaluated in the hippocampus by immunohistochemistry and ELISA, respectively. Behavioral tests showed that acute HH exposure caused the dysfunction of spatial memory and mood, while genetic inactivation of A 2A R attenuated the impairment of spatial memory but not that of mood. Double-labeled immunofluorescence showed that A 2A Rs were mainly expressed on microglia and up-regulated in the hippocampus of acute HH model mice. Acute HH also induced the accumulation of microglia and increased production of TNF-α in the hippocampus, which could be markedly inhibited by A 2A R inactivation. These findings indicate that microglia-mediated neuroinflammation triggered by A 2A R activation involves in acute HH-induced spatial memory impairment and that A 2A R could be a new target for the pharmacotherapy of cognitive dysfunction at high altitudes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01664328
- Volume :
- 347
- Database :
- Academic Search Index
- Journal :
- Behavioural Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 129922063
- Full Text :
- https://doi.org/10.1016/j.bbr.2018.02.038