Login Register Cart 0
Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Perspective

Noradrenaline and Seizures: A Perspective on the Role of Adrenergic Receptors in Limbic Seizures

Author(s): Francesca Biagioni, Roberta Celli, Stefano Puglisi-Allegra, Ferdinando Nicoletti, Filippo Sean Giorgi and Francesco Fornai*

Volume 21, Issue 11, 2023

Published on: 17 May, 2022

Page: [2233 - 2236] Pages: 4

DOI: 10.2174/1570159X20666220327213615

Abstract

Background: Noradrenergic fibers originating from the locus coeruleus densely innervate limbic structures, including the piriform cortex, which is the limbic structure with the lowest seizure threshold. Noradrenaline (NA) modulates limbic seizures while stimulating autophagy through β2- adrenergic receptors (AR). Since autophagy is related to seizure threshold, this perspective questions whether modulating β2-AR focally within the anterior piriform cortex affects limbic seizures.

Objective: In this perspective, we analyzed a potential role for β2-AR as an anticonvulsant target within the anterior piriform cortex, area tempestas (AT).

Methods: We developed this perspective based on current literature on the role of NA in limbic seizures and autophagy. The perspective is also grounded on preliminary data obtained by microinfusing within AT either a β2-AR agonist (salbutamol) or a β2-AR antagonist (butoxamine) 5 minutes before bicuculline.

Results: β2-AR stimulation fully prevents limbic seizures induced by bicuculline micro-infusion in AT. Conversely, antagonism at β2-AR worsens bicuculline-induced seizure severity and prolongs seizure duration, leading to self-sustaining status epilepticus. These data indicate a specific role for β2-AR as an anticonvulsant in AT.

Conclusion: NA counteracts limbic seizures. This relies on various receptors in different brain areas. The anterior piriform cortex plays a key role in patients affected by limbic epilepsy. The anticonvulsant effects of NA through β2-AR may be related to the stimulation of the autophagy pathway. Recent literature and present data draw a perspective where β2-AR stimulation while stimulating autophagy mitigates limbic seizures, focally within AT. The mechanism linking β2-AR to autophagy and seizure modulation should be extensively investigated.

Keywords: Area tempestas, piriform cortex, limbic seizures, noradrenaline, adrenergic receptors, β2-adrenergic receptors.

« Previous Next »
[1]
Engel, J., Jr A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia, 2001, 42(6), 796-803.
[http://dx.doi.org/10.1046/j.1528-1157.2001.10401.x] [PMID: 11422340]
[2]
Panayiotopoulos, C.P. A Clinical Guide to Epileptic Syndromes and their Treatment: Based on the New ILAE Diagnostic Scheme (first ed) Bladon Medical Publishing; Limited, Oxfordshire: UK, 2002.
[3]
McIntyre, D.C.; Giugno, L. Effect of clonidine on amygdala kindling in normal and 6-hydroxydopamine-pretreated rats. Exp. Neurol., 1988, 99(1), 96-106.
[http://dx.doi.org/10.1016/0014-4886(88)90130-6] [PMID: 2826214]
[4]
Shin, R.S.; McIntyre, D.C. Differential noradrenergic influence on seizure expression in genetically Fast and Slow kindling rat strains during massed trial stimulation of the amygdala. Neuropharmacology, 2007, 52(2), 321-332.
[http://dx.doi.org/10.1016/j.neuropharm.2006.08.004] [PMID: 17027042]
[5]
Dalton, J.C.; Roberts, D.C.; McIntyre, D.C. Supersensitivity to the anticonvulsant and proconvulsant activity of clonidine following noradrenaline depletion induced by 6-hydroxydopamine. Psychopharmacology (Berl.), 1985, 85(3), 319-322.
[http://dx.doi.org/10.1007/BF00428195] [PMID: 3923518]
[6]
McIntyre, D.C.; Kelly, M.E.; Dufresne, C. Suppression of amygdala kindling with massed stimulation: Effect of noradrenaline antagonists. Brain Res., 1991, 561(2), 279-284.
[http://dx.doi.org/10.1016/0006-8993(91)91605-Z] [PMID: 1802345]
[7]
McIntyre, D.C.; Rajala, J.; Edson, N. Suppression of amygdala kindling with short interstimulus intervals: Effect of norepinephrine depletion. Exp. Neurol., 1987, 95(2), 391-402.
[http://dx.doi.org/10.1016/0014-4886(87)90147-6] [PMID: 3803519]
[8]
McIntyre, D.C.; Edson, N. Kindling-based status epilepticus: Effect of norepinephrine depletion with 6-hydroxydopamine. Exp. Neurol., 1989, 104(1), 10-14.
[http://dx.doi.org/10.1016/0014-4886(89)90002-2] [PMID: 2494052]
[9]
McIntyre, D.C.; Saari, M.; Pappas, B.A. Potentiation of amygdala kindling in adult or infants rats by injections of 6-hydroxydopamine. Exp. Neurol., 1979, 63(3), 527-544.
[http://dx.doi.org/10.1016/0014-4886(79)90169-9] [PMID: 428481]
[10]
McIntyre, D.C.; Edson, N. Facilitation of amygdala kindling after norepinephrine depletion with 6-hydroxydopamine in rats. Exp. Neurol., 1981, 74(3), 748-757.
[http://dx.doi.org/10.1016/0014-4886(81)90248-X] [PMID: 6796430]
[11]
McIntyre, D.C. Amygdala kindling in rats: Facilitation after local amygdala norepinephrine depletion with 6-hydroxydopamine. Exp. Neurol., 1980, 69(2), 395-407.
[http://dx.doi.org/10.1016/0014-4886(80)90222-8] [PMID: 7409053]
[12]
Shin, R.S.; Anisman, H.; Merali, Z.; McIntyre, D.C. Amygdala amino acid and monoamine levels in genetically Fast and Slow kindling rat strains during massed amygdala kindling: A microdialysis study. Eur. J. Neurosci., 2004, 20(1), 185-194.
[http://dx.doi.org/10.1111/j.1460-9568.2004.03477.x] [PMID: 15245491]
[13]
Weinshenker, D.; Szot, P. The role of catecholamines in seizure susceptibility: New results using genetically engineered mice. Pharmacol. Ther., 2002, 94(3), 213-233.
[http://dx.doi.org/10.1016/S0163-7258(02)00218-8] [PMID: 12113799]
[14]
Giorgi, F.S.; Pizzanelli, C.; Biagioni, F.; Murri, L.; Fornai, F. The role of norepinephrine in epilepsy: From the bench to the bedside. Neurosci. Biobehav. Rev., 2004, 28(5), 507-524.
[http://dx.doi.org/10.1016/j.neubiorev.2004.06.008] [PMID: 15465138]
[15]
Straughan, D.W.; Neal, M.J.; Simmonds, M.A.; Collins, G.G.; Hill, R.G. Evaluation of bicuculline as a GABA antagonist. Nature, 1971, 233(5318), 352-354.
[http://dx.doi.org/10.1038/233352a0] [PMID: 4940434]
[16]
Giorgi, F.S.; Ferrucci, M.; Lazzeri, G.; Pizzanelli, C.; Lenzi, P.; Alessandrl, M.G.; Murri, L.; Fornai, F. A damage to locus coeruleus neurons converts sporadic seizures into self-sustaining limbic status epilepticus. Eur. J. Neurosci., 2003, 17(12), 2593-2601.
[http://dx.doi.org/10.1046/j.1460-9568.2003.02692.x] [PMID: 12823466]
[17]
Piredda, S.; Gale, K. A crucial epileptogenic site in the deep prepiriform cortex. Nature, 1985, 317(6038), 623-625.
[http://dx.doi.org/10.1038/317623a0] [PMID: 4058572]
[18]
Vismer, M.S.; Forcelli, P.A.; Skopin, M.D.; Gale, K.; Koubeissi, M.Z. The piriform, perirhinal, and entorhinal cortex in seizure generation. Front. Neural Circuits, 2015, 9, 27.
[http://dx.doi.org/10.3389/fncir.2015.00027] [PMID: 26074779]
[19]
Giorgi, F.S.; Biagioni, F.; Lenzi, P.; Frati, A.; Fornai, F. The role of autophagy in epileptogenesis and in epilepsy-induced neuronal alterations. J. Neural Transm. (Vienna), 2015, 122(6), 849-862.
[http://dx.doi.org/10.1007/s00702-014-1312-1] [PMID: 25217966]
[20]
Lazzeri, G.; Busceti, C.L.; Biagioni, F.; Fabrizi, C.; Morucci, G.; Giorgi, F.S.; Ferrucci, M.; Lenzi, P.; Puglisi-Allegra, S.; Fornai, F. Norepinephrine protects against methamphetamine toxicity through β2-adrenergic receptors promoting LC3 compartmentalization. Int. J. Mol. Sci., 2021, 22(13), 7232.
[http://dx.doi.org/10.3390/ijms22137232] [PMID: 34281286]
[21]
Ghosh, A.; Mukherjee, B.; Chen, X.; Yuan, Q. β-Adrenoceptor activation enhances L-type calcium channel currents in anterior piriform cortex pyramidal cells of neonatal mice: Implication for odor learning. Learn. Mem., 2017, 24(3), 132-135.
[http://dx.doi.org/10.1101/lm.044818.116] [PMID: 28202717]
[22]
Biagioni, F.; Celli, R.; Giorgi, F.S.; Nicoletti, F.; Fornai, F. Perspective on mTOR-dependent protection in status epilepticus. Curr. Neuropharmacol., 2021.
[http://dx.doi.org/10.2174/1570159X19666211005152618] [PMID: 34636300]
[23]
Fornai, F.; Busceti, C.L.; Kondratyev, A.; Gale, K. AMPA receptor desensitization as a determinant of vulnerability to focally evoked status epilepticus. Eur. J. Neurosci., 2005, 21(2), 455-463.
[http://dx.doi.org/10.1111/j.1460-9568.2005.03873.x] [PMID: 15673444]
[24]
Abd-Elrahman, K.S.; Hamilton, A.; Vasefi, M.; Ferguson, S.S.G. Autophagy is increased following either pharmacological or genetic silencing of mGluR5 signaling in Alzheimer’s disease mouse models. Mol. Brain, 2018, 11(1), 19.
[http://dx.doi.org/10.1186/s13041-018-0364-9] [PMID: 29631635]
[25]
Giorgi, F.S.; Blandini, F.; Cantafora, E.; Biagioni, F.; Armentero, M.T.; Pasquali, L.; Orzi, F.; Murri, L.; Paparelli, A.; Fornai, F. Activation of brain metabolism and fos during limbic seizures: The role of locus coeruleus. Neurobiol. Dis., 2008, 30(3), 388-399.
[http://dx.doi.org/10.1016/j.nbd.2008.02.008] [PMID: 18395460]
[26]
Shehata, M.; Matsumura, H.; Okubo-Suzuki, R.; Ohkawa, N.; Inokuchi, K. Neuronal stimulation induces autophagy in hippocampal neurons that is involved in AMPA receptor degradation after chemical long-term depression. J. Neurosci., 2012, 32(30), 10413-10422.
[http://dx.doi.org/10.1523/JNEUROSCI.4533-11.2012] [PMID: 22836274]
[27]
Galovic, M.; Baudracco, I.; Wright-Goff, E.; Pillajo, G.; Nachev, P.; Wandschneider, B.; Woermann, F.; Thompson, P.; Baxendale, S.; McEvoy, A.W.; Nowell, M.; Mancini, M.; Vos, S.B.; Winston, G.P.; Sparks, R.; Prados, F.; Miserocchi, A.; de Tisi, J.; Van Graan, L.A.; Rodionov, R.; Wu, C.; Alizadeh, M.; Kozlowski, L.; Sharan, A.D.; Kini, L.G.; Davis, K.A.; Litt, B.; Ourselin, S.; Moshé, S.L.; Sander, J.W.A.; Löscher, W.; Duncan, J.S.; Koepp, M.J. Association of piriform cortex resection with surgical outcomes in patients with temporal lobe epilepsy. JAMA Neurol., 2019, 76(6), 690-700.
[http://dx.doi.org/10.1001/jamaneurol.2019.0204] [PMID: 30855662]

Rights & Permissions Print Cite
Article Metrics
5
© 2024 Bentham Science Publishers | Privacy Policy