Open AccessAmyloid β induces interneuron-specific changes in the hippocampus of APPNL-F mice
Author(s) -
Katalin E. Sos,
Márton I. Mayer,
Virág T. Takács,
Ábel Major,
Zsuzsanna Bardóczi,
Barnabas M. Beres,
Tamás Szeles,
Takashi Saito,
Takaomi C. Saido,
István Módy,
Tamás F. Freund,
Gábor Nyíri
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0233700
Subject(s) - parvalbumin , interneuron , hippocampal formation , neuroscience , biology , hippocampus , cognitive decline , perineuronal net , axon , microglia , amyloid (mycology) , medicine , immunology , inflammation , dementia , inhibitory postsynaptic potential , botany , disease
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and amyloid-beta (Aβ) depositions generated by the proteolysis of amyloid precursor protein (APP) in the brain. In APP NL-F mice, APP gene was humanized and contains two familial AD mutations, and APP–unlike other mouse models of AD–is driven by the endogenous mouse APP promoter. Similar to people without apparent cognitive dysfunction but with heavy Aβ plaque load, we found no significant decline in the working memory of adult APP NL-F mice, but these mice showed decline in the expression of normal anxiety. Using immunohistochemistry and 3D block-face scanning electron microscopy, we found no changes in GABA A receptor positivity and size of somatic and dendritic synapses of hippocampal interneurons. We did not find alterations in the level of expression of perineuronal nets around parvalbumin (PV) interneurons or in the density of PV- or somatostatin-positive hippocampal interneurons. However, in contrast to other investigated cell types, PV interneuron axons were occasionally mildly dystrophic around Aβ plaques, and the synapses of PV-positive axon initial segment (AIS)-targeting interneurons were significantly enlarged. Our results suggest that PV interneurons are highly resistant to amyloidosis in APP NL-F mice and amyloid-induced increase in hippocampal pyramidal cell excitability may be compensated by PV-positive AIS-targeting cells. Mechanisms that make PV neurons more resilient could therefore be exploited in the treatment of AD for mitigating Aβ-related inflammatory effects on neurons.