Epilepsy is characterized by an imbalance in neurotransmitter activity; an increased excitatory to an inhibitory activity. Acetylcholine (ACh), serotonin, and norepinephrine (NE) may modulate neural activity via several mechanisms, mainly through its receptors/transporter activity and alterations in the extracellular potassium (K+) concentration via K+ ion channels. Seizures may disrupt the regulation of inwardly rectifying K+ (Kir) channels and alter the receptor/transporter activity. However, there are limited data present on the immunoreactivity pattern of these neurotransmitter receptors/transporters and K+ channels in chronic models of epilepsy, which therefore was the aim of this study. Changes in the immunoreactivity of epileptogenesis-related neurotransmitter receptors/transporters (M2, 5-HT2B, and NE transporter) as well as Kir channels (Kir3.1 and Kir6.2) were determined in the cortex, hippocampus and medulla of adultWistar rats by utilizing a Pentylenetetrazol (PTZ)-kindling chronic epilepsy model. Increased immunoreactivity of the NE transporter, M2, and 5-HT2B receptors was witnessed in the cortex and medulla. While the immunoreactivity of the 5-HT2B receptor was found increased in the cortex and medulla, it was decreased in the hippocampus, with no changes observed in the M2 receptor in this region. Kir3.1 and Kir6.2 staining showed increase immunoreactivity in the cerebral cortex, but channel contrasting findings in the hippocampus and medulla. Our results suggest that seizure kindling may result in significant changes in the neurotransmitter system which may contribute or propagate to future epileptogenesis, brain damage and potentially towards sudden unexpected death in epilepsy (SUDEP). Further studies on the pathogenic role of these changes in neurotransmitter receptors/transporters and K+ channel immunoreactivity may identify newer possible targets to treat seizures or prevent epilepsy-related comorbidities.

Akyuz, E., Doganyigit, Z., Paudel, Y., Koklu, B., Kaymak, E., Villa, C., et al. (2021). Immunoreactivity of muscarinic acetylcholine M2 and serotonin 5-HT2B receptors, norepinephrine transporter and kir channels in a model of epilepsy. LIFE, 11(4) [10.3390/life11040276].

Immunoreactivity of muscarinic acetylcholine M2 and serotonin 5-HT2B receptors, norepinephrine transporter and kir channels in a model of epilepsy

Villa C.;
2021

Abstract

Epilepsy is characterized by an imbalance in neurotransmitter activity; an increased excitatory to an inhibitory activity. Acetylcholine (ACh), serotonin, and norepinephrine (NE) may modulate neural activity via several mechanisms, mainly through its receptors/transporter activity and alterations in the extracellular potassium (K+) concentration via K+ ion channels. Seizures may disrupt the regulation of inwardly rectifying K+ (Kir) channels and alter the receptor/transporter activity. However, there are limited data present on the immunoreactivity pattern of these neurotransmitter receptors/transporters and K+ channels in chronic models of epilepsy, which therefore was the aim of this study. Changes in the immunoreactivity of epileptogenesis-related neurotransmitter receptors/transporters (M2, 5-HT2B, and NE transporter) as well as Kir channels (Kir3.1 and Kir6.2) were determined in the cortex, hippocampus and medulla of adultWistar rats by utilizing a Pentylenetetrazol (PTZ)-kindling chronic epilepsy model. Increased immunoreactivity of the NE transporter, M2, and 5-HT2B receptors was witnessed in the cortex and medulla. While the immunoreactivity of the 5-HT2B receptor was found increased in the cortex and medulla, it was decreased in the hippocampus, with no changes observed in the M2 receptor in this region. Kir3.1 and Kir6.2 staining showed increase immunoreactivity in the cerebral cortex, but channel contrasting findings in the hippocampus and medulla. Our results suggest that seizure kindling may result in significant changes in the neurotransmitter system which may contribute or propagate to future epileptogenesis, brain damage and potentially towards sudden unexpected death in epilepsy (SUDEP). Further studies on the pathogenic role of these changes in neurotransmitter receptors/transporters and K+ channel immunoreactivity may identify newer possible targets to treat seizures or prevent epilepsy-related comorbidities.
Articolo in rivista - Articolo scientifico
5-HT2B; Chronic epilepsy; M2; Norepinephrine; PTZ;
English
26-mar-2021
2021
11
4
276
open
Akyuz, E., Doganyigit, Z., Paudel, Y., Koklu, B., Kaymak, E., Villa, C., et al. (2021). Immunoreactivity of muscarinic acetylcholine M2 and serotonin 5-HT2B receptors, norepinephrine transporter and kir channels in a model of epilepsy. LIFE, 11(4) [10.3390/life11040276].
File in questo prodotto:
File Dimensione Formato  
10281-310980_VoR.pdf

accesso aperto

Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Licenza: Creative Commons
Dimensione 4.89 MB
Formato Adobe PDF
4.89 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/310980
Citazioni
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 6
Social impact