Hydrogen sulfide attenuates lipopolysaccharide-induced cognitive impairment: a pro-inflammatory pathway in rats.
The present study investigated the effect of sodium hydrosulfide (NaHS), a H(2)S donor, on cognitive impairment and neuroinflammatory changes induced by bilateral intracerebroventricular injections of LPS at a dose of 10mug/rat. Rats received 5mg/kg NaHS or volume-matched vehicle administration by intraperitoneal injection 3days before LPS injection then for 9days once daily. Morris water maze was used to detect the cognitive function. Compared to the sham-treated rats, LPS injection significantly prolonged the mean escape latency in the navigation test (P<0.05) and shortened the adjusted escape latency by approximately 30% (P<0.05). Meanwhile, LPS injection decreased H(2)S level but increased pro-inflammatory mediators (i.e., TNF-alpha, TNFR1, degradation of IkappaB-alpha and thereafter activation of NF-kappaB) in hippocampus. However, these effects of LPS were significantly ameliorated with NaHS treatment (P<0.05 vs vehicle-treated group). The present data suggest that H(2)S attenuates LPS-induced cognitive impairment through reducing the overproduction of pro-inflammatory mediators via inhibition of NF-kappaB pathways in rats. This study sets the stage for exploring a novel H(2)S releasing agent for preventing or retarding the development or progression of neurological disorders such as Alzheimer's disease.
Gong
Qi-Hai
QH
Department of Pharmacology, School of Pharmacy, Fudan University and Institute of Biomedical Sciences, Shanghai 201203, China.
Wang
Qian
Q
Pan
Li-Long
LL
Liu
Xin-Hua
XH
Huang
Hui
H
Zhu
Yi-Zhun
YZ
D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D006862:Hydrogen Sulfide