. 2020 Jul 7;21(13):4812. doi: 10.3390/ijms21134812

Table 3.

Effects of neuroactive steroids on impaired neurogenesis and memory in AD models.

Impaired Neurogenesis	Aβ-Induced Memory Loss
• Male APPswe/PS1dE9 mice PREGS ↑ survival & maturation of newborn cells [137] Allopregnanolone 10 mg/kg 1/week/6 months at 3 months of age ↑ survival of newly generated cells in hippocampal subgranular zone [86] • Rat B104 neuroblastoma cells PREGS or DHEAS 5 µM, 24 h ↓ Aβ_25–35 (20 µM)-induced decrease in neurite outgrowth [78] • 3 xTg-AD mice aged 6 and 9 months Allopregnanolone 10 mg/kg s.c. ↑ neurogenesis (BrDU⁺ neural progenitor survival) 1 h later [157]	• Male healthy mice + aggregated Aβ_25–35 (3 nmol i.c.v) PREGS, DHEAS, DHEA (5, 10, 20 mg/kg s.c. respectively) ↓memory Aβ-induced deficits in short-term memory (spontaneous alternation in the Y-maze test) and in long-term memory (step-down passive avoidance test), 7 and 14 days post-Aβ infusion, respectively, through σ1 receptor activation [154] • Male healthy mice + aggregated Aβ_25–35 (9 nmol i.c.v) Pretreatment by PREGS or DHEAS 0.5 nmol i.c.v 6 h before Aβ infusion ↓ memory deficits in short-term memory (spontaneous alternation test) and in long-term memory (step-through passive avoidance test) [78] • Ovariectomized APPswe/PS1dE9 mice PROG pellet (25 mg, 90-day release) ↑ short-term memory performance (object recognition T-maze test) [156] Allopreganolone (4.7 nmol or 9.3 nmol) for 12 weeks ↑ learning deficits in the Morris water maze [84] •3 xTg-AD mice aged 6 & 9 months Allopregnanolone 10 mg/kg s.c. 7 days prior to the start of the learning trials restored maximal learning capacity in the trace eyeblink conditioning, except at 12 months of age [157]

Impaired Neurogenesis

Aβ-Induced Memory Loss

• Male APPswe/PS1dE9 mice

PREGS ↑ survival & maturation of newborn cells [137]

Allopregnanolone 10 mg/kg 1/week/6 months at 3 months of age
↑ survival of newly generated cells in hippocampal subgranular zone
[86]

• Rat B104 neuroblastoma cells
PREGS or DHEAS 5 µM, 24 h
↓ Aβ_25–35 (20 µM)-induced decrease in neurite outgrowth [78]

• 3 xTg-AD mice aged 6 and 9 months
Allopregnanolone 10 mg/kg s.c.
↑ neurogenesis (BrDU⁺ neural progenitor survival) 1 h later [157]

• Male healthy mice + aggregated Aβ_25–35 (3 nmol i.c.v)
PREGS, DHEAS, DHEA (5, 10, 20 mg/kg s.c. respectively)
↓memory Aβ-induced deficits in short-term memory (spontaneous alternation in the Y-maze test) and in long-term memory (step-down passive avoidance test), 7 and 14 days post-Aβ infusion, respectively, through σ1 receptor activation [154]

• Male healthy mice + aggregated Aβ_25–35 (9 nmol i.c.v) Pretreatment by PREGS or DHEAS 0.5 nmol i.c.v
6 h before Aβ infusion
↓ memory deficits in short-term memory (spontaneous alternation test) and in long-term memory (step-through passive avoidance test) [78]

• Ovariectomized APPswe/PS1dE9 mice
PROG pellet (25 mg, 90-day release)
↑ short-term memory performance (object recognition T-maze test) [156]

Allopreganolone (4.7 nmol or 9.3 nmol) for 12 weeks
↑ learning deficits in the Morris water maze [84]

•3 xTg-AD mice aged 6 & 9 months
Allopregnanolone 10 mg/kg s.c. 7 days prior to the start of the learning trials
restored maximal learning capacity in the trace eyeblink conditioning, except at 12 months of age [157]

↓ decrease, ↑ increase vs. Aβ condition.