期刊
NEUROSCIENCE
卷 499, 期 -, 页码 142-151出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2022.07.020
关键词
Lithium-pilocarpine; Epilepsy; SV2A; [3H]-UCB-J; Autoradiography
资金
- Scientific and Technological Research Council of Turkey
- European Seventh's Framework Programme (FP7/2007- 2013) [602102]
The study reveals that the binding capacity of vesicle glycoprotein 2A (SV2A) is significantly reduced in the cerebral cortex and hippocampus after epilepsy occurs, while no significant changes are observed in the thalamus and hypothalamus. The regions with larger and earlier reductions include the hippocampus and piriform cortex. Interestingly, the binding capacity returns to control levels 12 weeks after the status epilepticus, similar to the chronic epileptic phase.
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.(c) 2022 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
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