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Contribution of early Alzheimer's disease‐related pathophysiology to the development of acquired epilepsy
Author(s) -
Gschwind Tilo,
Lafourcade Carlos,
Gfeller Tim,
Zaichuk Mariana,
Rambousek Lukas,
Knuesel Irene,
Fritschy JeanMarc
Publication year - 2018
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13983
Subject(s) - epileptogenesis , status epilepticus , epilepsy , kainic acid , neurogenesis , neuroscience , neuroinflammation , neurodegeneration , pathophysiology , biology , medicine , endocrinology , disease , glutamate receptor , receptor
Aberrant epileptic activity is detectable at early disease stages in Alzheimer's disease ( AD ) patients and in AD mouse models. Here, we investigated in young ArcticAβ mice whether AD ‐like pathology renders neuronal networks more susceptible to the development of acquired epilepsy induced by unilateral intrahippocampal injection of kainic acid ( IHK ). In this temporal lobe epilepsy model, IHK induces a status epilepticus followed after two weeks by spontaneous recurrent seizures ( SRS ). ArcticAβ mice exhibited more severe status epilepticus and early onset of SRS . This hyperexcitable phenotype was characterized in CA 1 neurons by decreased synaptic strength, increased kainic acid‐induced LTP and reduced frequency of spontaneous inhibitory currents. However, no difference in neurodegeneration, neuroinflammation, axonal reorganization or adult neurogenesis was observed in ArcticAβ mice compared to wild‐type littermates following IHK ‐induced epileptogenesis. Neuropeptide Y ( NPY ) expression was reduced at baseline and its IHK ‐induced elevation in mossy fibres and granule cells was attenuated. However, although this alteration might underlie premature seizure onset, neutralization of soluble Aβ species by intracerebroventricular Aβ‐specific antibody application mitigated the hyperexcitable phenotype of ArcticAβ mice and prevented early SRS onset. Therefore, the development of seizures at early stages of AD is mediated primarily by Aβ species causing widespread changes in synaptic function.