Spatio-Temporal Alterations in Synaptic Density During Epileptogenesis in the Rat Brain
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Spatio-Temporal Alterations in Synaptic Density During Epileptogenesis in the Rat Brain. / Mikkelsen, Jens D.; Aripaka, Sanjay S.; Bascuñana, Pablo; Bankstahl, Marion; Bankstahl, Jens P.; Pazarlar, Burcu A.
In: Neuroscience, Vol. 499, 2022, p. 142-151.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Spatio-Temporal Alterations in Synaptic Density During Epileptogenesis in the Rat Brain
AU - Mikkelsen, Jens D.
AU - Aripaka, Sanjay S.
AU - Bascuñana, Pablo
AU - Bankstahl, Marion
AU - Bankstahl, Jens P.
AU - Pazarlar, Burcu A.
N1 - Publisher Copyright: © 2022 The Authors
PY - 2022
Y1 - 2022
N2 - Synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein that binds levetiracetam and is involved in neurotransmission via an unknown mechanism. SV2A-immunoreactivity is reduced in animal models of epilepsy, and in postmortem hippocampi from patients with temporal lobe epilepsy. It is not known if other regions outside the hippocampus are affected in epilepsy, and whether SV2A expression is permanently reduced or regulated over time. In this study, we induced a generalized status epilepticus (SE) by systemic administration of lithium-pilocarpine to adult female rats. The brains from all animals experiencing SE were collected at different time points after the treatment. The radiotracer, [11C]-UCB-J, binds to SV2A with high affinity, and has been used for in vivo imaging as an a-proxy marker for synaptic density. Here we determined the level of tritiated UCB-J binding by semiquantitative autoradiography in the cerebral cortex, hippocampus, thalamus, and hypothalamus, and in cortical subregions. A prominent and highly significant reduction in SV2A binding capacity was observed over the first days after SE in the cerebral cortex and the hippocampus, but not in the thalamus and hypothalamus. The magnitude in reduction was larger and occurred earlier in the hippocampus and the piriform cortex, than in other cortical subregions. Interestingly, in all areas examined, the binding capacity returned to control levels 12 weeks after the SE comparable to the chronic epileptic phase. These data indicate that lithium-pilocarpine-induced epileptogenesis involves both loss and gain of synapses in the in a time-dependent manner.
AB - Synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein that binds levetiracetam and is involved in neurotransmission via an unknown mechanism. SV2A-immunoreactivity is reduced in animal models of epilepsy, and in postmortem hippocampi from patients with temporal lobe epilepsy. It is not known if other regions outside the hippocampus are affected in epilepsy, and whether SV2A expression is permanently reduced or regulated over time. In this study, we induced a generalized status epilepticus (SE) by systemic administration of lithium-pilocarpine to adult female rats. The brains from all animals experiencing SE were collected at different time points after the treatment. The radiotracer, [11C]-UCB-J, binds to SV2A with high affinity, and has been used for in vivo imaging as an a-proxy marker for synaptic density. Here we determined the level of tritiated UCB-J binding by semiquantitative autoradiography in the cerebral cortex, hippocampus, thalamus, and hypothalamus, and in cortical subregions. A prominent and highly significant reduction in SV2A binding capacity was observed over the first days after SE in the cerebral cortex and the hippocampus, but not in the thalamus and hypothalamus. The magnitude in reduction was larger and occurred earlier in the hippocampus and the piriform cortex, than in other cortical subregions. Interestingly, in all areas examined, the binding capacity returned to control levels 12 weeks after the SE comparable to the chronic epileptic phase. These data indicate that lithium-pilocarpine-induced epileptogenesis involves both loss and gain of synapses in the in a time-dependent manner.
KW - Autoradiography
KW - Epilepsy
KW - Lithium-pilocarpine
KW - SV2A
KW - [H]-UCB-J
U2 - 10.1016/j.neuroscience.2022.07.020
DO - 10.1016/j.neuroscience.2022.07.020
M3 - Journal article
C2 - 35878719
AN - SCOPUS:85135856550
VL - 499
SP - 142
EP - 151
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
ER -
ID: 317563362