Mitchell Center for Neurodegenerative Diseases, Department of Neurology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Department of Radiation Oncology, University of California, Irvine, CA 92697, USA.
Int J Mol Sci. 2021 Apr 1;22(7):3668. doi: 10.3390/ijms22073668.
The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/rat) studies reported impaired associative memory formation in both species following a chronic 6-month low dose exposure to a mixed field of neutrons (1 mGy/day for a total dose pf 18 cGy). In the present study, we report neutron exposure induced synaptic plasticity in the medial prefrontal cortex, accompanied by microglial activation and significant synaptic loss in the hippocampus. In a parallel study, neutron exposure was also found to alter fluorescence assisted single synaptosome LTP (FASS-LTP) in the hippocampus of rats, that may be related to a reduced ability to insert AMPAR into the post-synaptic membrane, which may arise from increased phosphorylation of the serine 845 residue of the GluA1 subunit. Thus, we demonstrate for the first time, that low dose chronic neutron irradiation impacts homeostatic synaptic plasticity in the hippocampal-cortical circuit in two rodent species, and that the ability to successfully encode associative recognition memory is a dynamic, multicircuit process, possibly involving compensatory changes in AMPAR density on the synaptic surface.
拟议的深空探测月球,之后探测火星,将导致宇航员受到大量慢性太空辐射(SR)暴露。SR 暴露会导致多种神经认知障碍。最近,我们的跨物种(小鼠/大鼠)研究报告称,在慢性 6 个月低剂量混合中子场暴露(每天 1 mGy,总剂量为 18 cGy)后,两种物种的联想记忆形成均受损。在本研究中,我们报告了中前额叶皮层中的突触可塑性,伴随着小胶质细胞的激活和海马体中的显著突触丢失。在一项平行研究中,还发现中子暴露改变了大鼠海马体中的荧光辅助单个突触长时程增强(FASS-LTP),这可能与 AMPAR 插入突触后膜的能力降低有关,这可能源于 GluA1 亚基丝氨酸 845 残基的磷酸化增加。因此,我们首次证明,低剂量慢性中子辐照会影响两种啮齿动物海马-皮质回路中的稳态突触可塑性,并且成功编码联想识别记忆的能力是一个动态的、多回路过程,可能涉及突触表面上 AMPAR 密度的代偿性变化。