Abstract
The objective of this study was to characterize the impact of allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, on interictal spikes and high-frequency oscillations (ripples: 80–200 Hz, fast ripples: 250–500 Hz) in the pilocarpine model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats experiencing 1 h of pilocarpine-induced status epilepticus (SE) began treatment with allopregnanolone (9.6–12.8 mg/kg/day) on the following day. On day 4 after SE, video-depth EEG recordings from the hippocampal CA3 subfield and the entorhinal cortex were initiated and continued for 12 consecutive days. We found that 66.7% (12/18) of untreated animals exhibited seizures compared to 28.6% (2/7) of allopregnanolone-treated animals. Interictal spikes occurred less frequently in the CA3 subfield of allopregnanolone-treated rats (n = 4) than in untreated animals presenting (n = 4) or not presenting (n = 4) with spontaneous seizures (p < 0.05), and were less frequent in the entorhinal cortex compared to both untreated groups (p < 0.05). Finally, allopregnanolone-treated rats had significantly lower rates of interictal spikes with fast ripples (250–500 Hz) compared to untreated animals but only in CA3 (p < 0.05). Our findings show that allopregnanolone reduces the frequency of interictal spikes and fast ripples in CA3, a structure that plays an important role in ictogenesis and epileptogenesis. Neurosteroids may therefore influence pathological network activity leading to spontaneous seizures following pilocarpine-induced SE. Recordings after termination of allopregnanolone treatment will be however required to establish whether allopregnanolone exerts disease-modifying properties.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12-19 |
| Number of pages | 8 |
| Journal | Neuropharmacology |
| Volume | 121 |
| DOIs | |
| State | Published - Jul 15 2017 |
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Keywords
- Allopregnanolone
- High-frequency oscillations
- Mesial temporal lobe epilepsy
- Neurosteroids
- Pilocarpine
ASJC Scopus subject areas
- Pharmacology
- Cellular and Molecular Neuroscience
Cite this
Allopregnanolone decreases interictal spiking and fast ripples in an animal model of mesial temporal lobe epilepsy. / Lévesque, Maxime; Herrington, Rochelle; Leclerc, Leila; Rogawski, Michael A; Avoli, Massimo.
In: Neuropharmacology, Vol. 121, 15.07.2017, p. 12-19.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Allopregnanolone decreases interictal spiking and fast ripples in an animal model of mesial temporal lobe epilepsy
AU - Lévesque, Maxime
AU - Herrington, Rochelle
AU - Leclerc, Leila
AU - Rogawski, Michael A
AU - Avoli, Massimo
PY - 2017/7/15
Y1 - 2017/7/15
N2 - The objective of this study was to characterize the impact of allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, on interictal spikes and high-frequency oscillations (ripples: 80–200 Hz, fast ripples: 250–500 Hz) in the pilocarpine model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats experiencing 1 h of pilocarpine-induced status epilepticus (SE) began treatment with allopregnanolone (9.6–12.8 mg/kg/day) on the following day. On day 4 after SE, video-depth EEG recordings from the hippocampal CA3 subfield and the entorhinal cortex were initiated and continued for 12 consecutive days. We found that 66.7% (12/18) of untreated animals exhibited seizures compared to 28.6% (2/7) of allopregnanolone-treated animals. Interictal spikes occurred less frequently in the CA3 subfield of allopregnanolone-treated rats (n = 4) than in untreated animals presenting (n = 4) or not presenting (n = 4) with spontaneous seizures (p < 0.05), and were less frequent in the entorhinal cortex compared to both untreated groups (p < 0.05). Finally, allopregnanolone-treated rats had significantly lower rates of interictal spikes with fast ripples (250–500 Hz) compared to untreated animals but only in CA3 (p < 0.05). Our findings show that allopregnanolone reduces the frequency of interictal spikes and fast ripples in CA3, a structure that plays an important role in ictogenesis and epileptogenesis. Neurosteroids may therefore influence pathological network activity leading to spontaneous seizures following pilocarpine-induced SE. Recordings after termination of allopregnanolone treatment will be however required to establish whether allopregnanolone exerts disease-modifying properties.
AB - The objective of this study was to characterize the impact of allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, on interictal spikes and high-frequency oscillations (ripples: 80–200 Hz, fast ripples: 250–500 Hz) in the pilocarpine model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats experiencing 1 h of pilocarpine-induced status epilepticus (SE) began treatment with allopregnanolone (9.6–12.8 mg/kg/day) on the following day. On day 4 after SE, video-depth EEG recordings from the hippocampal CA3 subfield and the entorhinal cortex were initiated and continued for 12 consecutive days. We found that 66.7% (12/18) of untreated animals exhibited seizures compared to 28.6% (2/7) of allopregnanolone-treated animals. Interictal spikes occurred less frequently in the CA3 subfield of allopregnanolone-treated rats (n = 4) than in untreated animals presenting (n = 4) or not presenting (n = 4) with spontaneous seizures (p < 0.05), and were less frequent in the entorhinal cortex compared to both untreated groups (p < 0.05). Finally, allopregnanolone-treated rats had significantly lower rates of interictal spikes with fast ripples (250–500 Hz) compared to untreated animals but only in CA3 (p < 0.05). Our findings show that allopregnanolone reduces the frequency of interictal spikes and fast ripples in CA3, a structure that plays an important role in ictogenesis and epileptogenesis. Neurosteroids may therefore influence pathological network activity leading to spontaneous seizures following pilocarpine-induced SE. Recordings after termination of allopregnanolone treatment will be however required to establish whether allopregnanolone exerts disease-modifying properties.
KW - Allopregnanolone
KW - High-frequency oscillations
KW - Mesial temporal lobe epilepsy
KW - Neurosteroids
KW - Pilocarpine
UR - http://www.scopus.com/inward/record.url?scp=85018341084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018341084&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2017.04.020
DO - 10.1016/j.neuropharm.2017.04.020
M3 - Article
C2 - 28416442
AN - SCOPUS:85018341084
VL - 121
SP - 12
EP - 19
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
ER -