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Table 2 Female studies of cognition & behavior in mouse models of AD

From: Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

Hormone/ Regimen Manipulation Timing, Route, Dose Comparison A Cognition & Behavioral Measure and Ref. AD Tg Model
Hormone Depletion Gnx 3 mos N/A Intact vs Gnx Gnx ↓ SAB (Y-maze) [162, 163] 3xTg-AD
Gnx ↓ open arm time (EPM) [164]
Gnx 3 mos N/A Intact vs Gnx Gnx ↔ spatial memory (MWM) [159] APP+PS1
  VCD 2-2.5 mos N/A Intact vs VCD VCD ↔ spatial/working memory (RAWM) [160] APPswe
Estrogens Gnx 3 mo Immediate s.c. E2 (0.025 mg) 90 d Gnx: Veh vs E2 E2 ↑ SAB (Y-maze) [162, 164] 3xTg-AD
E2 ↓ freezing (FST) [164]
Gnx 3 mos Immediate s.c. PPT (0.25 mg) 90 d Gnx: Veh vs PPT PPT ↑ SAB (Y-maze) [162] 3xTg-AD
Gnx 3 mos Immediate s.c. DPN (0.25 mg) 90 d Gnx: Veh vs DPN DPN ↔ SAB (Y-maze) [162] 3xTg-AD
Gnx 3 mos Immediate, 3, & 6 mo later, s.c. E2 (0.18 mg) Gnx vs Gnx + E2 E2 ↔ spatial memory (MWM) [159] APP+PS1
VCD 2-2.5 mos Immediate s.c. E2 (0.36 mg) 90 d VCD vs VCD+E2 E2 ↔ spatial/working memory (RAWM) [160] APPswe
P 4 Continuous Gnx 3 mos Immediate s.c. P4 (25 mg) 90 d Gnx: Veh vs P4 P4 ↔ SAB (Y-maze) [163, 164] 3xTg-AD
P4 ↑ open arm time, ↓ freezing (EPM, FST) [164]
Gnx 6 mos Immediate s.c. P4 (25 mg) 90+d Gnx vs Gnx + P4 P4↔ spatial memory (NPR, MWM) [169] APPswe+ PSEN1ΔE9
P 4 Cyclical Gnx 3 mos Delayed s.c. P4 (2.8 mg) 10 d off/on Gnx: Veh vs P4 P4 ↔ SAB (Y-maze) [164] 3xTg-AD
P4↑ open arm time, ↓ freezing (EPM, FST) [164]
E 2 + P 4 Continuous Gnx 3 mos Immediate s.c. E2 (0.025 mg) + P4 (25 mg) 90 d Gnx: Veh vs E2+ P4 E2+ P4 ↑ SAB (Y-maze) [163] 3xTg-AD
Gnx 3 mos Immediate s.c. E2 (0.025 mg) + P4(25 mg) 90 d Gnx: Veh vs E2+ P4 E2+ P4 ↔SAB (Y-maze) [164] 3xTg-AD
E2+P4 ↑ open arm time, ↓ freezing (FST, EPM) [164]
E 2 + P 4 Cyclical Gnx 3 mos Immediate s.c. E2 (0.025 mg) 90 d + P4 (2.8 mg) 30 d cycles Gnx: Veh vs E2+ P4 E2+ P4 ↑ SAB (Y-maze) [164] 3xTg-AD
E2+P4 ↑ open arm time, ↓ freezing (FST, EPM) [164]
LH Depletion 21 mos I.M. injection of leuprolide followed by depot (7.5 mg/kg) Intact: Veh vs leuprolide leuprolide ↑ SAB in aging (Y-maze) [180] Tg2576
Testosterone Postnatal d1–7 IP injection of T (100 μg/d) Intact: Veh vs T T↔SAB (Y-maze) [116] 3xTg-AD
  1. Symbols: ↑=increase, ↓=decrease, ↔=no change.
  2. Abbreviations: Tg=transgenic, mos=months, d=day, E 2 =estradiol (a type of estrogen), P 4 =progesterone, LH=Leutinizing hormone, VCD=4-vinylcyclohexene diepoxide (causes chemically-induced ovarian atrophy), s.c.=subcutaneous, I.M.=intramuscular, IP=intraperitoneal, SAB=spontaneous alternating behavior (thought to reflect working memory), FST=forced swim test, RAWM=radial arm water maze, NPR=novel place recognition, EPM=elevated plus maze, PPT= Propylpyrazole triol (ERα agonist), DPN= Diarylpropionitrile (ERβ agonist), leuprolide=leuprolide acetate (gonadotropin-releasing hormone agonist).
  3. A, All comparisons are between groups of AD Tg mice.