Open AccessA 2A R inhibition in alleviating spatial recognition memory impairment after TBI is associated with improvement in autophagic flux in RSC
Author(s) -
Zeng XuJia,
Li Ping,
Ning YaLei,
Zhao Yan,
Peng Yan,
Yang Nan,
Xu YaWei,
Chen JiangFan,
Zhou YuanGuo
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15361
Subject(s) - tfeb , retrosplenial cortex , chromatin structure remodeling (rsc) complex , autophagy , neuroscience , spatial memory , memory impairment , morris water navigation task , traumatic brain injury , downregulation and upregulation , chemistry , medicine , microbiology and biotechnology , psychology , biology , cortex (anatomy) , working memory , transcription factor , hippocampus , biochemistry , psychiatry , apoptosis , cognition , chromatin remodeling , gene
Spatial recognition memory impairment is an important complication after traumatic brain injury (TBI). We previously found that spatial recognition memory impairment can be alleviated in adenosine A 2A receptor knockout (A 2A R KO) mice after TBI, but the mechanism remains unclear. In the current study, we used manganese‐enhanced magnetic resonance imaging and the Y‐maze test to determine whether the electrical activity of neurons in the retrosplenial cortex (RSC) was reduced and spatial recognition memory was impaired in wild‐type (WT) mice after moderate TBI. Furthermore, spatial recognition memory was damaged by optogenetically inhibiting the electrical activity of RSC neurons in WT mice. Additionally, the electrical activity of RSC neurons was significantly increased and spatial recognition memory impairment was reduced in A 2A R KO mice after moderate TBI. Specific inhibition of A 2A R in the ipsilateral RSC alleviated the impairment in spatial recognition memory in WT mice. In addition, A 2A R KO improved autophagic flux in the ipsilateral RSC after injury. In primary cultured neurons, activation of A 2A R reduced lysosomal‐associated membrane protein 1 and cathepsin D (CTSD) levels, increased phosphorylated protein kinase A and phosphorylated extracellular signal‐regulated kinase 2 levels, reduced transcription factor EB (TFEB) nuclear localization and impaired autophagic flux. These results suggest that the impairment of spatial recognition memory after TBI may be associated with impaired autophagic flux in the RSC and that A 2A R activation may reduce lysosomal biogenesis through the PKA/ERK2/TFEB pathway to impair autophagic flux.