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_2AR 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_2AR KO mice after moderate TBI. Specific inhibition of A_2AR in the ipsilateral RSC alleviated the impairment in spatial recognition memory in WT mice. In addition, A_2AR KO improved autophagic flux in the ipsilateral RSC after injury. In primary cultured neurons, activation of A_2AR 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_2AR activation may reduce lysosomal biogenesis through the PKA/ERK2/TFEB pathway to impair autophagic flux.

中文翻译：

---

TBI后A2A R抑制可减轻空间识别记忆障碍与RSC自噬通量的改善有关。

空间识别记忆障碍是脑外伤（TBI）后的重要并发症。我们以前发现，腺苷A _2A受体基因敲除（A _2ATBI后的R KO）小鼠，但机制尚不清楚。在当前的研究中，我们使用锰增强磁共振成像和Y迷宫测试来确定在野生型（WT）小鼠中，脾后皮质（RSC）中神经元的电活动是否减少并且空间识别记忆受损中度TBI后。此外，光遗传抑制野生型小鼠的RSC神经元的电活动破坏了空间识别记忆。此外，中度TBI后，A _2A R KO小鼠的RSC神经元的电活动显着增加，空间识别记忆障碍减少。在同侧RSC中对A _2A R的特异性抑制减轻了WT小鼠空间识别记忆的损伤。另外，A _2AR KO改善了损伤后同侧RSC中的自噬通量。在原代培养的神经元中，激活A _2A R降低了溶酶体相关膜蛋白1和组织蛋白酶D（CTSD）的水平，增加了磷酸化蛋白激酶A和磷酸化的细胞外信号调节激酶2的水平，降低了转录因子EB（TFEB）的核定位和自噬通量受损。这些结果表明，TBI后空间识别记忆的损害可能与RSC中自噬通量受损有关，并且A _2A R激活可能通过PKA / ERK2 / TFEB途径减少了溶酶体生物发生，从而损害了自噬通量。