The effects of social environment on AD-related pathology in hAPP-J20 mice and tau-P301L mice

Suzanne D Lanooij; W H I M Drinkenburg; U L M Eisel; E A van der Zee; Martien J H Kas

doi:10.1016/j.nbd.2023.106309

The effects of social environment on AD-related pathology in hAPP-J20 mice and tau-P301L mice

Neurobiol Dis. 2023 Oct 15:187:106309. doi: 10.1016/j.nbd.2023.106309. Epub 2023 Sep 23.

Authors

Suzanne D Lanooij¹, W H I M Drinkenburg², U L M Eisel³, E A van der Zee⁴, Martien J H Kas⁵

Affiliations

¹ Groningen Institute for Evolutionary Life Sciences (GELIFES), Neurobiology, University of Groningen, Nijenborgh 7, 9747, AG, Groningen, the Netherlands. Electronic address: s.d.lanooij@rug.nl.
² Groningen Institute for Evolutionary Life Sciences (GELIFES), Neurobiology, University of Groningen, Nijenborgh 7, 9747, AG, Groningen, the Netherlands; Department of Neuroscience, Janssen Research & Development, a Division on Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. Electronic address: w.h.i.m.drinkenburg@rug.nl.
³ Groningen Institute for Evolutionary Life Sciences (GELIFES), Neurobiology, University of Groningen, Nijenborgh 7, 9747, AG, Groningen, the Netherlands. Electronic address: u.l.m.eisel@rug.nl.
⁴ Groningen Institute for Evolutionary Life Sciences (GELIFES), Neurobiology, University of Groningen, Nijenborgh 7, 9747, AG, Groningen, the Netherlands. Electronic address: e.a.van.der.zee@rug.nl.
⁵ Groningen Institute for Evolutionary Life Sciences (GELIFES), Neurobiology, University of Groningen, Nijenborgh 7, 9747, AG, Groningen, the Netherlands. Electronic address: m.j.h.kas@rug.nl.

PMID: 37748620
DOI: 10.1016/j.nbd.2023.106309

Abstract

In humans, social factors (e.g., loneliness) have been linked to the risk of developing Alzheimer's Disease (AD). To date, AD pathology is primarily characterized by amyloid-β plaques and tau tangles. We aimed to assess the effect of single- and group-housing on AD-related pathology in a mouse model for amyloid pathology (J20, and WT controls) and a mouse model for tau pathology (P301L) with and without seeding of synthetic human tau fragments (K18). Female mice were either single housed (SH) or group housed (GH) from the age of 6-7 weeks onwards. In 12-week-old P301L mice, tau pathology was induced through seeding by injecting K18 into the dorsal hippocampus (P301L_K18), while control mice received a PBS injection (P301L_PBS). P301L mice were sacrificed at 4 months of age and J20 mice at 10 months of age. In all mice brain pathology was histologically assessed by examining microglia, the CA1 pyramidal cell layer and specific AD pathology: analysis of plaques in J20 mice and tau hyperphosphorylation in P301L mice. Contrary to our expectation, SH-J20 mice interestingly displayed fewer plaques in the hippocampus compared to GH-J20 mice. However, housing did not affect tau hyperphosphorylation at Ser202/Thr205 of P301L mice, nor neuronal cell death in the CA1 region in any of the mice. The number of microglia was increased by the J20 genotype, and their activation (based on cell body to cell size ratio) in the CA1 was affected by genotype and housing condition (interaction effect). Single housing of P301L mice was linked to the development of stereotypic behavior (i.e. somersaulting and circling behavior). In P301L_K18 mice, an increased number of microglia were observed, among which were rod microglia. Taken together, our findings point to a significant effect of social housing conditions on amyloid plaques and microglia in J20 mice and on the development of stereotypic behavior in P301L mice, indicating that the social environment can modulate AD-related pathology.

Keywords: Alzheimer's disease; Amyloid pathology; Social environment; Social isolation; Tau pathology; Transgenic mice.