Partial depletion of septohippocampal cholinergic cells reduces seizure susceptibility, but does not mitigate hippocampal neurodegeneration in the kainate model of epilepsy

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Soares, JI (Author) Other; Da Costa, C (Author) Other; Ferreira, MH (Author) Other; Andrade, PA (Author) Other; Maia, GH (Author) Other; Lukoyanov, NV (Author) FMUP

Journal

Title: Brain Research

Vol. 1717

Pages: 235-246

ISSN: 0006-8993

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00Q-FWV

DOI: 10.1016/j.brainres.2019.04.027

Abstract (EN): The brain cholinergic system may undergo structural and functional alterations both in human epilepsy and in respective animal models, but the causal relationships between these alterations and epilepsy remain to be established. In this study, we attempted to examine how the inhibition of epilepsy-related cholinergic plasticity may be reflected in seizure susceptibility and/or in the development of chronic epilepsy and its neurological consequences. For this purpose, adult Wistar rats received intrahippocampal injections of low doses of 192-IgG-saporin (SAP) to produce a moderate, but significant loss of septohippocampal cholinergic cells and to suppress their plasticity. Then, animals were treated with kainic acid to induce status epilepticus, which leads to the development of chronic epilepsy later in life. It was found that SAP-pretreatment was associated with longer latency to the onset of status epilepticus and with reduced mortality rate, suggesting that increased activity of septal cholinergic cells may potentiate seizures. Interestingly, months later, a greater percentage of rats with intact septohippocampal cholinergic connections showed spontaneous seizures, when compared to SAP-pretreated rats. Treatment with kainic acid produced death of 40-50% of hippocampal neurons and this effect was not ameliorated by prior cholinergic depletion. Moreover, the kainate induced cognitive deficits were detected in both SAP-pretreated and sham-pretreated groups. These data suggest that seizure-induced plasticity of cholinergic cells may indeed enhance seizure susceptibility and contribute to epileptogenic processes. They do not support the hypothesis that epilepsy-related hypertrophy of cholinergic neurons may potentiate hippocampal cell loss and respective behavioral impairments.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12