Abstract
Hyperglutamatergic activity in the hippocampus is a major feature of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Here we investigated whether tonic α7 nicotinic receptor (nAChR) activity could contribute to enhanced glutamatergic activity in the hippocampus of patients with MTLE-HS. Results showed that frequency and amplitude of glutamatergic events recorded from pyramidal neurons in the hippocampal samples obtained from patients with MTLE-HS were altered by α7 nAChR antagonist, methyllycaconitine, suggesting α7 nAChRs may influence hyperexcitability in MTLE-HS.
This is a preview of subscription content, log in via an institution to check access.
References
Albuquerque EX, Pereira EFR, Alkondon M, Rogers SW (2009) Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev 89:73–120. https://doi.org/10.1152/physrev.00015.2008
Banerjee J, Alkondon M, Albuquerque EX (2012) Kynurenic acid inhibits glutamatergic transmission to CA1 pyramidal neurons via α7 nAChR-dependent and -independent mechanisms. Biochem Pharmacol 84:1078–1087. https://doi.org/10.1016/j.bcp.2012.07.030
Banerjee J, Dixit AB, Tripathi M, Sarkar C, Gupta YK, Chandra PS (2015) Enhanced endogenous activation of NMDA receptors in pyramidal neurons of hippocampal tissues from patients with mesial temporal lobe epilepsy: a mechanism of hyper excitation. Epilepsy Res 117:11–16. https://doi.org/10.1016/j.eplepsyres.2015.08.007
Banerjee J, Dixit AB, Srivastava A, Ramanujam B, Kakkar A, Sarkar C, Tripathi M, Chandra PS (2017) Altered glutamatergic tone reveals two distinct resting state networks at the cellular level in hippocampal sclerosis. Sci Rep 7:319. https://doi.org/10.1038/s41598-017-00358-7
Damaj MI, Glassco W, Dukat M, Martin BR (1999) Pharmacological characterization of nicotine-induced seizures in mice. J Pharmacol Exp Ther 291:1284–1291
Eid T, Williamson A, Lee TS, Petroff OA, de Lanerolle NC (2008) Glutamate and astrocytes-key players in human mesial temporal lobe epilepsy? Epilepsia 49(2):42–52. https://doi.org/10.1111/j.1528-1167.2008.01492.x
Gray R, Rajan AS, Radcliffe KA, Yakehiro M, Dani JA (1996) Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature 383:713–716. https://doi.org/10.1038/383713a0
Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M, Franke A, Muhle H, de Kovel C, Baker C, von Spiczak S, Kron KL, Steinich I, Kleefuss-Lie AA, Leu C, Gaus V, Schmitz B, Klein KM, Reif PS, Rosenow F, Weber Y, Lerche H, Zimprich F, Urak L, Fuchs K, Feucht M, Genton P, Thomas P, Visscher F, de Haan GJ, Møller RS, Hjalgrim H, Luciano D, Wittig M, Nothnagel M, Elger CE, Nürnberg P, Romano C, Malafosse A, Koeleman BP, Lindhout D, Stephani U, Schreiber S, Eichler EE, Sander T (2009) 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet 41:160–162. https://doi.org/10.1038/ng.292
Huang LT, Sherwood JL, Sun YJ, Lodge D, Wang Y (2010) Activation of presynaptic α7 nicotinic receptors evokes an excitatory response in hippocampal CA3 neurones in anaesthetized rats: an in vivo iontophoretic study. Br J Pharmacol 59:554–565. https://doi.org/10.1111/j.1476-5381.2009.00529.x
Konradsson-Geuken A, Gash CR, Alexander K, Pomerleau F, Huettl P, Gerhardt GA, Bruno JP (2009) Second-by-second analysis of α7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats. Synapse 63:1069–1082. https://doi.org/10.1002/syn.20693
Lӧscher W, Potschka H, Wlaz P, Danyz W, Parsons CG (2003) Are neuronal nicotinic receptors a target for antiepileptic drug development? Studies in different seizure models in mice and rats. Eur J Pharmacol 466:99–111. https://doi.org/10.1016/s0014-2999(03)01542-5
Steinlein OK (2002) Nicotinic acetylcholine receptors and epilepsy. Curr Drug Targets CNS Neurol Disord 1:443–448. https://doi.org/10.2174/1568007023339193
Acknowledgements
The authors are indebted to all the patients and their family for participating in this study.
Funding
This work was supported by Early Career Intramural Research Grant (IRG) from All India Institute of Medical Sciences (AIIMS), New Delhi, India [A-606].
Author information
Authors and Affiliations
Contributions
JB, ABD, PSC, and MT contributed to the conception and design of the study. JB, SD, RD, MCS, PSC, and MT contributed to the acquisition and analysis of data. JB, ABD, PSC, and MT contributed to drafting the text and preparing the figures. All authors have read and approved the final version of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Ethics statement
The study was approved by the institutional ethics committee (IEC), All India Institute of Medical Sciences (AIIMS), New Delhi, India. Written, informed consent was obtained for all the patients (IEC-190/RP27/2018).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Banerjee, J., Dey, S., Dixit, A.B. et al. α7 nicotinic receptors contributes to glutamatergic activity in the hippocampus of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). J Neural Transm 127, 1441–1446 (2020). https://doi.org/10.1007/s00702-020-02239-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-020-02239-2