Hormonal and biochemical changes in female Proechimys guyannensis, an animal model of resistance to pilocarpine-induced status epilepticus

Abstract

AbstractThe Amazon rodentProechimys guyannensisis widely studied for hosting various pathogens, though rarely getting sick. Previous studies on maleProechimyshave revealed an endogenous resistance to epilepsy. Here, we assess in femaleProechimys,whether sex hormones and biochemical aspects can interfere with the induction of status epilepticus (SE). The lithium-pilocarpine ramp-up protocol was used to induce SE, and blood sera were collected at 30 and 90 min after SE, alongside brains, for biochemical, western blot and immunohistochemical analyses. Results from non-ovariectomised (NOVX)Proechimyswere compared to ovariectomised (OVX) animals. Data from female Wistars were used as a positive control of SE inductions. SE latency was similar in NOVX, OVX, and female Wistars groups. However, the pilocarpine dose required to induce SE inProechimyswas higher (25- to 50-folds more). Despite a higher dose,Proechimysdid not show strong SE like Wistars; they only reached stage 2 of the Racine scale. These data suggest that femaleProechimysare resistant to SE induction. Glucose and progesterone levels increased at 30 min and returned to normal at 90 min after SE. A relevant fact because in humans and rodents, SE leads to hypoglycaemia after 30 min of SE and does not return to normal levels in a short time, a typical adverse effect of SE. In OVX animals, a decrease in GABAergic receptors within 90 min of SE may suggest that ovariectomy produces changes in the hippocampus, including a certain vulnerability to seizures. We speculate that progesterone and glucose increases form part of the compensatory mechanisms that provide resistance inProechimysagainst SE induction.