Background: Neurosteroids modulate epileptic activity by interacting with the γ-aminobutyric acid type A receptor, but their brain levels are still undetermined. Objectives: We aimed to establish levels of neurosteroids in the neocortex and hippocampus by liquid chromatography–mass spectrometry in epileptic rats. Methods: Kainic acid-treated rats were continuously monitored up to 9 weeks to determine the seizure frequency by video electrocorticography (n=23), and compared to age-matched controls monitored in the same manner (n=11). Results: A reduction in allopregnanolone (-50%; p<0.05, Mann-Whitney test) and pregnanolone levels (-64%; p<0.01) was found in the hippocampus, whereas pregnenolone sulfate, pregnenolone, progesterone, and 5α-dihydroprogesterone were nonsignificantly reduced. No changes were found in the neocortex. Moreover, allopregnanolone (but not pregnanolone) levels were positively correlated with the seizure frequency (r2=0.4606, p<0.01). Conclusions: These findings indicate a selective reduction in hippocampal levels of 3α-reduced neurosteroids. This reduction was partially mitigated by seizures in the case of allopregnanolone.
Allopregnanolone and pregnanolone are reduced in the hippocampus of epileptic rats, but only allopregnanolone correlates with the seizure frequency / Lucchi, Chiara; Costa, ANNA MARIA; Rustichelli, Cecilia; Biagini, Giuseppe. - In: NEUROENDOCRINOLOGY. - ISSN 0028-3835. - 111:6(2021), pp. 536-541. [10.1159/000509093]
Allopregnanolone and pregnanolone are reduced in the hippocampus of epileptic rats, but only allopregnanolone correlates with the seizure frequency
Lucchi Chiara;Costa Anna Maria;Rustichelli Cecilia;Biagini Giuseppe
2021
Abstract
Background: Neurosteroids modulate epileptic activity by interacting with the γ-aminobutyric acid type A receptor, but their brain levels are still undetermined. Objectives: We aimed to establish levels of neurosteroids in the neocortex and hippocampus by liquid chromatography–mass spectrometry in epileptic rats. Methods: Kainic acid-treated rats were continuously monitored up to 9 weeks to determine the seizure frequency by video electrocorticography (n=23), and compared to age-matched controls monitored in the same manner (n=11). Results: A reduction in allopregnanolone (-50%; p<0.05, Mann-Whitney test) and pregnanolone levels (-64%; p<0.01) was found in the hippocampus, whereas pregnenolone sulfate, pregnenolone, progesterone, and 5α-dihydroprogesterone were nonsignificantly reduced. No changes were found in the neocortex. Moreover, allopregnanolone (but not pregnanolone) levels were positively correlated with the seizure frequency (r2=0.4606, p<0.01). Conclusions: These findings indicate a selective reduction in hippocampal levels of 3α-reduced neurosteroids. This reduction was partially mitigated by seizures in the case of allopregnanolone.File | Dimensione | Formato | |
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