Cholinergic Signaling, Neural Excitability, and Epilepsy
Abstract
:1. Introduction
2. Cholinergic Signaling for Modulating Neural Excitability
2.1. Cholinergic Signaling in the Brain
2.2. mAChRs and Neural Excitability
2.3. nAChRs and Neural Excitability
3. Cholinergic Signaling in Epilepsy
3.1. mAChRs and Epilepsy
3.2. nAChRs and Epilepsy
3.3. Cholinergic Neurons Circuit in Epilepsy
4. Conclusions and Outlook
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Epilepsy Model | Time Point | Observations | References |
---|---|---|---|
Temporal lobes with complex partial seizures | Interictal period | The binding of mAChRs antagonist I-iododexetimide was decreased in the anterior hippocampus. | [31] |
Patients with drug-resistant focal temporal lobe epilepsy | Interictal period | M2 receptors always increased in various seizures including febrile seizure, hippocampal sclerosis, and other neocortical pathologies. | [38] |
Patients with intractable temporal lobe epilepsy | Interictal period | An enhancement of M2 receptors binding in the lateral amygdala nuclei of TLE patients, while binding to M3 receptors was reduced. | [40] |
Kainic acid | 3 days after injection of kainic acid | 1. The reduction of ChAT activity in the piriform cortex, amygdala, and nucleus basalis. 2. The reduction of AChE activity in the piriform cortex. 3. The decrease of mAChRs binding in the piriform cortex, amygdala, and nucleus basalis. 4. The decrease of Na+-dependent high-affinity choline uptake in the piriform cortex and amygdala. | [30] |
Pilocarpine | 30 min after administration of pilocarpine | 1. M1 KO mice did not display seizures and survived after pilocarpine administration. 2. M2-M5 KO mice all had a seizure (clonic seizures) and died within 1 h after pilocarpine administration. | [33] |
Pilocarpine | 45 min after administration of pilocarpine | The inability of pilocarpine to evoke seizures in both homozygous and heterozygous M1 mutant mice. | [34] |
Pilocarpine | 45 min after administration of pilocarpine | 1. VU0255035 suppresses the potentiation of NMDAR currents induced by carbachol in hippocampal pyramidal cells. 2. VU0255035 inhibits pilocarpine-induced seizures. | [36] |
OPs | 60 min after administration of OPs | VU0255035 retarded the process of status epilepticus after OPs exposure. | [37] |
PTZ kindling model | 30 min after administration of PTZ | The increase of M2 receptors was observed in PTZ-kindled in the brainstem. | [39] |
PTZ kindling model | 180 and 240 min after administration of PTZ | Sparteine increases the hippocampal M4 receptor expression. | [41] |
Epilepsy Model | Time Point | Observations | References |
---|---|---|---|
Patients with mesial temporal lobe epilepsy with hippocampal sclerosis | Interictal period | α7 nAChRs were found to regulate hyperfunction of glutamatergic synaptic transmission in the hippocampus. | [52] |
HEK293 cells co-expressing the human α4 nAChRs and the wild-type and the V287L mutant patient | - | 1. The mutant in β2V287L presynaptic nAChRs triggering neuronal firing, serving as an enhancement of neurotransmitter release. 2. The abnormal mutant in postsynaptic nAChRs may cause hyperexcitability. | [53] |
Reconstituted in Xenopus oocytes | - | 100 μM CBZ inhibits ACh-evoked currents at the human α4β2 nicotinic receptors, and the ADSHE α4S248F or α4L-776ins3 mutant receptors, with a roughly 3 fold increase in sensitivity to CBZ. | [55] |
ADSHE patients | Interictal period | An increase of midbrain nAChRs density in the ADSHE. | [56] |
Patients with insular epilepsy | Interictal period | Mutant nACh receptors increased nicotinic currents in whole-cell recording. | [57] |
Genetic or focal epilepsy with febrile seizures (GEFS+) patients | Interictal period | CHRNA4 was the pathogenic gene of GEFS+. | [58] |
Familial partial epilepsy with variable foci (FPEVF) patients | Interictal period | cHRNA4 was the pathogenic gene of FPEVF. | [59] |
Nicotine | Intraperitoneally injected 15 min before the nicotine treatment. | Nicotine elicits convulsive seizures by activating amygdalar neurons mainly via α7 nACh receptors. | [48] |
PTZ kindling | Exposed to PTZ injections on day 3, 6, and 9 of treatment to assess seizure severity score. | The amelioration of epilepsy by α7 nAChRs agonist choline chloride in PTZ-kindled mice model. | [50] |
MES and nicotine-induced seizure test in mice;Amygdala-kindling in rats. | 1.Nicotine-induced seizure starting immediately after nicotine injection and up to 5 min afterwards. 2. MES and kindling assesed interictal period. | 1. Various novel amino-alkyl-cyclohexane derivatives, among which nAChRs antagonists have shown an overlap potency between channel blocking at nAChRs and NMDARs. 2. nAChRs preferring antagonists were strongly relived MES and nicotine-induced seizure in mice. 3. The effect of anticonvulsant in the MES was all reduced by an additional injection of a subconvulsant dose of nicotine. 4. Such efficacious anticonvulsants were not affected in kindled rats | [51] |
Pilocarpine | EEG activities recorded 7 days post-surgical recovery | 1. Chat-Mecp2−/y mice displayed frequent hyperexcitability discharges. 2. Administration of pilocarpine produces status epilepticus in Chat-Mecp2−/y mice. 3. Administration of α7 nAChRs agonist PNU282987 in the CA1 of the hippocampus increased the seizures onset time. | [61] |
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Wang, Y.; Tan, B.; Wang, Y.; Chen, Z. Cholinergic Signaling, Neural Excitability, and Epilepsy. Molecules 2021, 26, 2258. https://doi.org/10.3390/molecules26082258
Wang Y, Tan B, Wang Y, Chen Z. Cholinergic Signaling, Neural Excitability, and Epilepsy. Molecules. 2021; 26(8):2258. https://doi.org/10.3390/molecules26082258
Chicago/Turabian StyleWang, Yu, Bei Tan, Yi Wang, and Zhong Chen. 2021. "Cholinergic Signaling, Neural Excitability, and Epilepsy" Molecules 26, no. 8: 2258. https://doi.org/10.3390/molecules26082258