Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
Department of Neurosurgery, Stanford University, Palo Alto, CA 94305, USA; Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Exp Neurol. 2018 Jul;305:44-55. doi: 10.1016/j.expneurol.2018.03.009. Epub 2018 Mar 11.
Of the many perils associated with deep space travel to Mars, neurocognitive complications associated with cosmic radiation exposure are of particular concern. Despite these realizations, whether and how realistic doses of cosmic radiation cause cognitive deficits and neuronal circuitry alterations several months after exposure remains unclear. In addition, even less is known about the temporal progression of cosmic radiation-induced changes transpiring over the duration of a time period commensurate with a flight to Mars. Here we show that rodents exposed to the second most prevalent radiation type in space (i.e. helium ions) at low, realistic doses, exhibit significant hippocampal and cortical based cognitive decrements lasting 1 year after exposure. Cosmic-radiation-induced impairments in spatial, episodic and recognition memory were temporally coincident with deficits in cognitive flexibility and reduced rates of fear extinction, elevated anxiety and depression like behavior. At the circuit level, irradiation caused significant changes in the intrinsic properties (resting membrane potential, input resistance) of principal cells in the perirhinal cortex, a region of the brain implicated by our cognitive studies. Irradiation also resulted in persistent decreases in the frequency and amplitude of the spontaneous excitatory postsynaptic currents in principal cells of the perirhinal cortex, as well as a reduction in the functional connectivity between the CA1 of the hippocampus and the perirhinal cortex. Finally, increased numbers of activated microglia revealed significant elevations in neuroinflammation in the perirhinal cortex, in agreement with the persistent nature of the perturbations in key neuronal networks after cosmic radiation exposure. These data provide new insights into cosmic radiation exposure, and reveal that even sparsely ionizing particles can disrupt the neural circuitry of the brain to compromise cognitive function over surprisingly protracted post-irradiation intervals.
在火星深空旅行中，有许多与宇宙辐射有关的危险，其中与神经认知并发症相关的危险尤其令人担忧。尽管已经认识到了这一点，但目前尚不清楚现实剂量的宇宙辐射是否以及如何导致暴露后数月的认知缺陷和神经元电路改变。此外，关于宇宙辐射引起的变化在与飞往火星相当的时间段内的时间进程，人们知之甚少。在这里，我们表明，暴露于太空中第二常见辐射类型（即氦离子）的低剂量、现实剂量的啮齿动物表现出明显的海马体和皮质基认知能力下降，持续 1 年暴露后。宇宙辐射引起的空间、情景和识别记忆损伤与认知灵活性缺陷以及恐惧消退减少、焦虑和抑郁样行为增加的时间一致。在电路水平上，照射导致了边缘皮层中主要细胞的固有特性（静息膜电位、输入电阻）发生显著变化，边缘皮层是我们认知研究中涉及的大脑区域。照射还导致边缘皮层主细胞的自发性兴奋性突触后电流的频率和幅度持续下降，以及海马体 CA1 与边缘皮层之间的功能连接减少。最后，激活的小胶质细胞数量的增加表明边缘皮层的神经炎症显著升高，这与宇宙辐射暴露后关键神经元网络的持续扰动一致。这些数据提供了对宇宙辐射暴露的新见解，并表明即使是稀疏电离粒子也会破坏大脑的神经回路，从而在令人惊讶的长时间的辐射后间隔内损害认知功能。
