Plastic rearrangement of basal forebrain parvalbumin-immunoreactive neurons in the kainite model of epilepsy

Ruben Carvalho; Alisa N. Lukoyanova; João Casalta-Lopes; Nikolay V. Lukoyanov; Joana Isabel Soares; Ruben Carvalho; Alisa N. Lukoyanova; João Casalta-Lopes; Nikolay V. Lukoyanov; Joana Isabel Soares

doi:10.3934/Neuroscience.2023023

AIMS Neuroscience

2023, Volume 10, Issue 4: 300-314. doi: 10.3934/Neuroscience.2023023

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Research article

Plastic rearrangement of basal forebrain parvalbumin-immunoreactive neurons in the kainite model of epilepsy

1.
Master in Neurobiology, Faculty of Medicine, University of Porto, Porto, Portugal
2.
Neuronal Networks Group, Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal
3.
Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal
4.
Department of Basic Sciences, Polytechnic Institute of Coimbra, Coimbra Health School, Coimbra, Portugal
5.
Life and Health Sciences Research Institute / School of Medicine - University of Minho, Braga, Portugal
6.
Department of Radiotherapy, University Hospital Center of São João, Porto, Portugal
These authors equally contributed to this work

Received: 15 August 2023 Revised: 21 October 2023 Accepted: 27 October 2023 Published: 02 November 2023

Temporal lobe epilepsy (TLE) is the most prevalent form of epilepsy, through the neuronal mechanisms of this syndrome remain elusive. In addition to the temporal lobe structures, it was found that the basal forebrain cholinergic cells are also involved in epileptogenesis. However, little is known about the involvement of the basal forebrain GABAergic neurons in epilepsy; despite this, they largely project to the temporal lobe and are crucial for the regulation of the hippocampal circuitry. In this study, we assessed epilepsy-induced changes in parvalbumin (PARV) immunoreactive neurons of the medial septum (MS) and of the magnocellular preoptic nucleus (MCPO) using the kainic acid (KA) model in rats. In addition, we estimated the respective changes in the cholinergic varicosities in the MS, where we observed a significant reduction in the PARV cell number (12849 ± 2715 vs. 9372 ± 1336, p = .029) and density (16.2 ± 2.62 vs. 10.5 ± 1.00 per .001 mm³, p =.001), and an increase in the density of cholinergic varicosities (47.9 ± 11.1 vs. 69.4 ± 17.8 per 30,000 µm², p =.036) in KA-treated animals. In the MCPO, these animals showed a significant increase in somatic volume (827.9 ± 235.2 µm³ vs. 469.9 ± 79.6 µm³, p = .012) and total cell number (2268.6 ± 707.1 vs. 1362.4 ± 262.0, p =.028). These results show that the basal forebrain GABAergic cell populations undergo numerical and morphological changes in epileptic animals, which may contribute to an increased vulnerability of brain circuits to epilepsy and epilepsy-related functional impairments.
- temporal lobe epilepsy,
- kainic-acid model,
- magnocellular preoptic nucleus,
- medial septum,
- parvalbumin,
- neurophysiology
Citation: Ruben Carvalho, Alisa N. Lukoyanova, João Casalta-Lopes, Nikolay V. Lukoyanov, Joana Isabel Soares. Plastic rearrangement of basal forebrain parvalbumin-immunoreactive neurons in the kainite model of epilepsy[J]. AIMS Neuroscience, 2023, 10(4): 300-314. doi: 10.3934/Neuroscience.2023023

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Abstract

Temporal lobe epilepsy (TLE) is the most prevalent form of epilepsy, through the neuronal mechanisms of this syndrome remain elusive. In addition to the temporal lobe structures, it was found that the basal forebrain cholinergic cells are also involved in epileptogenesis. However, little is known about the involvement of the basal forebrain GABAergic neurons in epilepsy; despite this, they largely project to the temporal lobe and are crucial for the regulation of the hippocampal circuitry. In this study, we assessed epilepsy-induced changes in parvalbumin (PARV) immunoreactive neurons of the medial septum (MS) and of the magnocellular preoptic nucleus (MCPO) using the kainic acid (KA) model in rats. In addition, we estimated the respective changes in the cholinergic varicosities in the MS, where we observed a significant reduction in the PARV cell number (12849 ± 2715 vs. 9372 ± 1336, p = .029) and density (16.2 ± 2.62 vs. 10.5 ± 1.00 per .001 mm³, p =.001), and an increase in the density of cholinergic varicosities (47.9 ± 11.1 vs. 69.4 ± 17.8 per 30,000 µm², p =.036) in KA-treated animals. In the MCPO, these animals showed a significant increase in somatic volume (827.9 ± 235.2 µm³ vs. 469.9 ± 79.6 µm³, p = .012) and total cell number (2268.6 ± 707.1 vs. 1362.4 ± 262.0, p =.028). These results show that the basal forebrain GABAergic cell populations undergo numerical and morphological changes in epileptic animals, which may contribute to an increased vulnerability of brain circuits to epilepsy and epilepsy-related functional impairments.

Abbreviations

ANOVA

Analysis of variance

Basal forebrain

Dorsal raphe

Hippocampal formation

Kainic acid

LDT

Laterodorsal tegmental nucleus

MANOVA

Multivariate analysis of variance

MCPO

Magnocellular preoptic nucleus

Medial septum nucleus

mTOR

Mammalian target of the rapamycin signalling pathway

NHS

Normal horse serum

PARV

Parvalbumin

PARV-IR

Parvalbumin-immunoreactive

PBS

Phosphate-buffered saline

PPN

Pedunculopontine nucleus

Status epilepticus

TLE

Temporal lobe epilepsy

Acknowledgments

This work was funded by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the Project UIDB/04293/2020. It was also supported by National Funds through FCT within the scopes of the Project PTDC/SAU-NSC/115506/2009 (Nikolay V. Lukoyanov) and of the Project SFRH/BD/ 87886/2012 (Joana Isabel Soares).

Conflict of interest

All authors declare no conflict of interest in this paper.

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