Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease

Table 3

Environmental enrichment in transgenic transgenic mouse models of Alzheimer’s disease.

Mouse model	Exposure	Duration of the exposure	Age at the start	Effect on brain	Effect on behavior	Reference
APPswe	Enriched housing (multiple mice in a large bin containing an inner cage with platforms, passageways, running wheels, toys, and novel habitats) + novel complex environment 3x weekly for several hours	4 months	16 months	No differences in total A𝛽 load	Improved MWM performance	[91]
TgCRND8	Enriched housing (equipped with diverse physically and cognitively stimulating objects, for example, gnawing wood, tunnels, balls, running wheels, and ladders)	4 months	1 month	↑ angiogenesis; ↑ ApoE, LRP1, A2M; ↓ RAGE	Not measured	[92]
TgCRND8	Enriched housing (equipped with diverse physically and cognitively stimulating objects, for example, gnawing wood, tunnels, balls, running wheels, and ladders)	4 months	1 month	↑ BrdU-positive cells; ↑ synaptophysin immunoreactivity in the hippocampus	Not measured	[93]
TgCRND8	Enriched housing (plastic inset, wooden climbing frame, and a nesting material)	4 months	1 month	Not measured	↑ exploratory behavior; ↓ anxiety-related behavior; No effects in learning and memory,; as assessed with MWM, barrier test, open-field, elevated plus maze, object recognition task, and Barnes maze	[94]
APP23	Enriched environment (multiple mice housed in large cages with a rearrangeable system of plastic tubes and cardboard boxes)	1 months	6, 18 months	No differences in plaque load; ↑ DCX/CR ratio; ↑ DCX- and calretinin-positive neurons in the hippocampus		[95]
APP23	Enriched housing (spacious cage equipped with a rearrangeable system of tubes, a cardboard box house, wire mesh ladders, and a crawling ball)	9 months	2 months	No differences in plaque load in neocortex or hippocampus; ↑ hippocampal neurogenesis (DCX, calretinin); ↑ BDNF, NT-3 in the hippocampus	Improved learning and memory in MWM	[96]
APPswe/PS1ΔE9	Enriched housing (multiple mice in a large cage with crawl-tubes, platforms, running wheels and toys, changed weekly)	6 months	1.5 month	↓ total A𝛽 deposition, 28% in the hippocampus and 36% in entorhinal cortex; ↑ synaptophysin in CA1 and CA3	Improved performance in MWM, RAWM	[97]
APPswe/PS1ΔE9	Enriched environment (large cages, running wheels, colored tunnels, toys, and chewable material)	1 month, 3 hours daily, next 4 months three times per week	1 month	↓ neocortical and hippocampal A𝛽 deposits; ↑ increased neprilysin expression	Not measured	[98]
PS1/PDAPP	Enriched housing (multiple mice in a large bin containing an inner cage with platforms, passageways, running wheels, toys, and novel habitats) + novel complex environment 3/weekly for several hours	5 months	weaning	↑ gene expression of TTR, NF-𝜅B inhibitors,	Improved performance in MWM, RAWM and platform recognition tasks	[99]
APPswe/PS1ΔE9	Enriched housing (larger cages with running wheels, plastic play tubes, cardboard boxes, and nesting material that were changes or rearranged weekly)	6 months	2 months	↑ 68% of plaque area in the hippocampus; ↑ 52% of total A𝛽 in hippocampus	Not measured	[100]
APPswe/PS1ΔE9	Enriched housing (larger cages with running wheels, plastic play tubes, cardboard boxes, and nesting material that were changes or rearranged weekly)	6 months	2 months	↑ 50% A𝛽42 in the hippocampus; ↑ 25% in hippocampal plaque load	Improved performance in MWM, RAWM	[101]
APOE3, APOE4	Cages with exploratory objects (toys, tunnels, and running wheels)	5 months	3 weeks	improvement in T-maze performance in APOE3 only	↑ expression of NGF; ↑ Synaptophysin in the hippocampus of APOE3 only	[102]
APOE3, APOE4	Enriched housing ( cage with running wheel, labyrinth, bedding, house, chains, and wooden blocks)	5 months	3 weeks	↑ hippocampal A𝛽 deposits in the APOE4	Not measured	[103]
APOE3, APOE4	Wheel running	6 weeks	10 months	↑ BDNF in both; ↑ TrkB, PAK and synaptophysin only in APOE4	Improved performance in place recognition in both genotypes; Improved RAWM in APOE4 only	[104]