Higher susceptibility of the ventral versus the dorsal hippocampus and the posteroventral versus anterodorsal amygdala to soman-induced neuropathology

Abstract

Nerve agents are acetylcholinesterase inhibitors, exposure to which causes brain damage, primarily by inducing intense seizure activity. Knowledge of the brain regions that are most vulnerable to nerve agent-induced brain damage can facilitate the development of drugs targeting the protection of these regions. Both the amygdala and the hippocampus have been shown to suffer significant damage after nerve agent exposure, but the amygdala appears to be the more severely affected structure. However, damage in the amygdala has generally been compared with damage in the dorsal hippocampus, whereas there is evidence that the ventral hippocampus is significantly more susceptible to seizures than the dorsal region and, therefore, it may also be more susceptible to nerve agent-induced neuropathology. Here, we report that after status epilepticus induced by soman administration to rats, neuronal degeneration as assessed by Fluoro-Jade C staining was more extensive in the ventral than the dorsal hippocampal subfields, 1 day after soman exposure. Seven days later, the difference between dorsal and ventral regions was not statistically significant. In the amygdala, soman-induced neurodegeneration was more severe in the posteroventral regions of the lateral, basolateral, and medial nuclei compared to the anterodorsal regions of these nuclei. In contrast, the basomedial nucleus was more severely affected in the anterodorsal region. The extent of neurodegeneration in the amygdala was not significantly different from that in the ventral hippocampus. However, when compared with the whole hippocampus, the amygdala displayed more severe neurodegeneration, on both day 1 and day 7 after soman exposure. Testing the protective efficacy of drugs against nerve agent-induced brain damage should include examination of the ventral hippocampus and the posteroventral regions of the amygdala, as these areas are most vulnerable to nerve agent-induced neurodegeneration.