Long-term molecular effects of ¹⁶O-ion exposure in rat brain and implications for space radiation risk

Exposure to high-energy charged particles like ¹⁶O ions poses risks to brain function during deep space travel. This study examined long-term neuroinflammatory and synaptic changes in rats 6 months after low-dose total-body ¹⁶O irradiation (1 cGy and 10 cGy), focusing on the frontal cortex, striatum, hippocampus, and thalamus. Using Western blotting, qPCR, and digital PCR, we assessed expression levels of neuroinflammatory (GFAP and IBA1) and synaptic (GAP43, PSD95, SYP, SPINO, and GPHN) markers. Correlation analyses to examine the relationship between the assessed molecular changes and behavioral performance in social odor recognition and psychomotor vigilance tasks were performed. In the hippocampus, 1 cGy exposure resulted in increased IBA1, GAP43, and PSD95, whereas 10 cGy exposure led to decreased GFAP and increased PSD95, SPINO, and GPHN. In the striatum, synaptic markers were elevated after both 1 cGy and 10 cGy exposure, though region-specific differences in gene expression levels were observed (qPCR/dPCR). In the frontal cortex, no changes across any of the targeted markers were detected, except for increased SYP in 1 cGy rats. In the thalamus, GFAP was reduced in 10 cGy rats, while GAP43 was increased in 1 cGy and PSD95 was increased in both 1 cGy and 10 cGy exposed animals. Correlation analyses revealed significant associations between molecular changes and behavior, including a negative correlation between hippocampal SYP protein levels and social memory performance in the 1 cGy group. Taken together, these results suggest dose- and region-specific brain responses to low-dose ¹⁶O ion exposure-a vital component of space radiation-culminating in an enhanced synaptic remodeling and possible neurological alterations. The data also highlight potential molecular mechanisms underlying region-based (i.e., striatum) cognitive vulnerability following low-dose particle exposure.