Table 2.

Neuroactive steroid protective effects on Aβ-induced neuroinflammation.

Steroid Treatment	Models of Aβ-induced Inflammation	Inflammatory Response against Aβ Neurotoxicity
PROG Pretreatment 4, 8 or 16 mg/kg, i.p. daily, for 7 and 12 days after Aβ injection	In vivo Male rats + aggregated Aβ25–35 5 µM in the hippocampal CA1 region	↓ the upregulation of TNFα and IL-1β induced by Aβ [43] ↓ endoplasmic reticulum stress markers PERK/elF2α
E2 pretreatment pellets 0.01 mg s.c. daily, from 5 to 10–14 months of age   E2 pretreatment 100 nM, 48 h   E2 pretreatment 10 µM, 60 min	In vivo Ovariectomized APP23 mice, 10–14 months of age (early stage of disease)   In vitro Human cortical microglia + fluorescein-Aβ1–42 100 nM   Microglial BV-2 cell + aggregated Aβ1–42 1 µM	↓ Mac-1 positive inflammatory plaques ↑ microglia clearance of Aβ [125]   ↑ microglia uptake of Aβ, through non-classical estrogen receptor [126]   ↓ Aβ-induced NF-κB [125,127]
Pretreatment Testosterone 100 nM Dihydrotestosterone 10 nM   Pretreatment Testosterone 200 µg Dihydrotestosterone 100 µg s.c. every day for 2 weeks   Pretreatment Dihydrotestosterone0.5 and 1 nM for 6 h	Murine microglia N9 cell line + aggregated Aβ1–42 (2 µM) for 30 min   Male C57BL/6 mice + aggregated Aβ1–42 (1 µM) into the CA1 region   Murine microglia N9 cell line + aggregated Aβ1–42 1 µM for 1 h or 24 h	↓ Aβ-induced proinflammatory cytokine IL-1β via suppression of NF-κB and p38 activation by Aβ [128]   ↓ Aβ-induced proinflammatory cytokine IL-1β [128]   ↑ microglia Aβ uptake through upregulating FPR2 ↑ microglia clearance of Aβ through upregulating ECE-1c [128]

↓ decrease, ↑ increase vs. Aβ condition.