Sulforaphane Ameliorates Okadaic Acid-Induced Memory Impairment in Rats by Activating the Nrf2/HO-1 Antioxidant Pathway

被引：59

作者：

Dwivedi, Subhash ^{[1
]}

Rajasekar, N. ^{[1
,3
]}

Hanif, Kashif ^{[1
,3
]}

Nath, Chandishwar ^{[2
,3
]}

Shukla, Rakesh ^{[1
,3
]}

机构：

[1] CSIR Cent Drug Res Inst, Div Pharmacol, Lucknow 226031, Uttar Pradesh, India

[2] CSIR Cent Drug Res Inst, Div Toxicol, Lucknow 226031, Uttar Pradesh, India

[3] Acad Sci & Innovat Res AcSIR, Madras, Tamil Nadu, India

来源：

MOLECULAR NEUROBIOLOGY | 2016年 / 53卷 / 08期

关键词：

Nrf2; Sulforaphane; Neuroinflammation; Memory impairment; Okadaic acid; Astrocytes; NF-KAPPA-B; TRANSCRIPTION FACTOR NRF2; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; DIABETIC-NEUROPATHY; PROTEIN-KINASE; CELL-DEATH; IN-VIVO; BRAIN; PROTECTION;

D O I：

10.1007/s12035-015-9451-4

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Okadaic acid (OKA) causes memory impairment and attenuates nuclear factor erythroid 2-related factor 2 (Nrf2) along with oxidative stress and neuroinflammation in rats. Sulforaphane (dietary isothiocyanate compound), an activator of Nrf2 signaling, exhibits neuroprotective effects. However, the protective effect of sulforaphane in OKA-induced neurotoxicity remains uninvestigated. Therefore, in the present study, the role of sulforaphane in OKA-induced memory impairment in rats was explored. A significant increased Nrf2 expression in the hippocampus and cerebral cortex was observed in trained (Morris water maze) rats, and a significant decreased Nrf2 expression in memory-impaired (OKA, 200 ng icv) rats indicated its involvement in memory function. Sulforaphane administration (5 and 10 mg/kg, ip, days 1 and 2) ameliorates OKA-induced memory impairment in rats. The treatment also restored Nrf2 and its downstream antioxidant protein expression (GCLC, HO-1) and attenuated oxidative stress (ROS, nitrite, GSH), neuroinflammation (NF-kappa B, TNF-alpha, IL-10), and neuronal apoptosis in the cerebral cortex and hippocampus of OKA-treated rats. Further, to determine whether modulation of Nrf2 signaling is responsible for the protective effect of sulforaphane, in vitro, Nrf2 siRNA and its downstream HO-1 inhibition studies were carried out in a rat astrocytoma cell line (C6). The protective effects of sulforaphane were abolished with Nrf2 siRNA and HO-1 inhibition in astrocytes. The results suggest that Nrf2-dependent activation of cellular antioxidant machinery results in sulforaphane-mediated protection against OKA-induced memory impairment in rats.

引用

页码：5310 / 5323

页数：14

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