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Hydrogen sulfide attenuates spatial memory impairment and hippocampal neuroinflammation in β-amyloid rat model of Alzheimer's disease.
J Neuroinflammation. 2012 Aug 17; 9:202.JN

Abstract

BACKGROUND

Endogenously produced hydrogen sulfide (H(2)S) may have multiple functions in brain. An increasing number of studies have demonstrated its anti-inflammatory effects. In the present study, we investigated the effect of sodium hydrosulfide (NaHS, a H(2)S donor) on cognitive impairment and neuroinflammatory changes induced by injections of Amyloid-β(1-40) (Aβ(1-40)), and explored possible mechanisms of action.

METHODS

We injected Aβ(1-40) into the hippocampus of rats to mimic rat model of Alzheimer's disease (AD). Morris water maze was used to detect the cognitive function. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to detect neuronal apoptosis. Immunohistochemistry analyzed the response of glia. The expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α was measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of Aβ(1-40), phospho-p38 mitogen-activated protein kinase (MAPK), phospho-p65 Nuclear factor (NF)-κB, and phospho-c-Jun N-terminal Kinase (JNK) was analyzed by western blot.

RESULTS

We demonstrated that pretreatment with NaHS ameliorated learning and memory deficits in an Aβ(1-40) rat model of AD. NaHS treatment suppressed Aβ(1-40)-induced apoptosis in the CA1 subfield of the hippocampus. Moreover, the over-expression in IL-1β and TNF-α as well as the extensive astrogliosis and microgliosis in the hippocampus induced by Aβ(1-40) were significantly reduced following administration of NaHS. Concomitantly, treatment with NaHS alleviated the levels of p38 MAPK and p65 NF-κB phosphorylation but not JNK phosphorylation that occurred in the Aβ(1-40)-injected hippocampus.

CONCLUSIONS

These results indicate that NaHS could significantly ameliorate Aβ(1-40)-induced spatial learning and memory impairment, apoptosis, and neuroinflammation at least in part via the inhibition of p38 MAPK and p65 NF-κB activity, suggesting that administration of NaHS could provide a therapeutic approach for AD.

Authors+Show Affiliations

Department of Anatomy, Guangzhou Medical University, Guangzhou, China. xag2005@sohu.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22898621

Citation

Xuan, Aiguo, et al. "Hydrogen Sulfide Attenuates Spatial Memory Impairment and Hippocampal Neuroinflammation in Β-amyloid Rat Model of Alzheimer's Disease." Journal of Neuroinflammation, vol. 9, 2012, p. 202.
Xuan A, Long D, Li J, et al. Hydrogen sulfide attenuates spatial memory impairment and hippocampal neuroinflammation in β-amyloid rat model of Alzheimer's disease. J Neuroinflammation. 2012;9:202.
Xuan, A., Long, D., Li, J., Ji, W., Zhang, M., Hong, L., & Liu, J. (2012). Hydrogen sulfide attenuates spatial memory impairment and hippocampal neuroinflammation in β-amyloid rat model of Alzheimer's disease. Journal of Neuroinflammation, 9, 202.
Xuan A, et al. Hydrogen Sulfide Attenuates Spatial Memory Impairment and Hippocampal Neuroinflammation in Β-amyloid Rat Model of Alzheimer's Disease. J Neuroinflammation. 2012 Aug 17;9:202. PubMed PMID: 22898621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrogen sulfide attenuates spatial memory impairment and hippocampal neuroinflammation in β-amyloid rat model of Alzheimer's disease. AU - Xuan,Aiguo, AU - Long,Dahong, AU - Li,Jianhua, AU - Ji,Weidong, AU - Zhang,Meng, AU - Hong,Lepeng, AU - Liu,Jihong, Y1 - 2012/08/17/ PY - 2012/05/08/received PY - 2012/08/04/accepted PY - 2012/8/18/entrez PY - 2012/8/18/pubmed PY - 2013/6/19/medline SP - 202 EP - 202 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 9 N2 - BACKGROUND: Endogenously produced hydrogen sulfide (H(2)S) may have multiple functions in brain. An increasing number of studies have demonstrated its anti-inflammatory effects. In the present study, we investigated the effect of sodium hydrosulfide (NaHS, a H(2)S donor) on cognitive impairment and neuroinflammatory changes induced by injections of Amyloid-β(1-40) (Aβ(1-40)), and explored possible mechanisms of action. METHODS: We injected Aβ(1-40) into the hippocampus of rats to mimic rat model of Alzheimer's disease (AD). Morris water maze was used to detect the cognitive function. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to detect neuronal apoptosis. Immunohistochemistry analyzed the response of glia. The expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α was measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of Aβ(1-40), phospho-p38 mitogen-activated protein kinase (MAPK), phospho-p65 Nuclear factor (NF)-κB, and phospho-c-Jun N-terminal Kinase (JNK) was analyzed by western blot. RESULTS: We demonstrated that pretreatment with NaHS ameliorated learning and memory deficits in an Aβ(1-40) rat model of AD. NaHS treatment suppressed Aβ(1-40)-induced apoptosis in the CA1 subfield of the hippocampus. Moreover, the over-expression in IL-1β and TNF-α as well as the extensive astrogliosis and microgliosis in the hippocampus induced by Aβ(1-40) were significantly reduced following administration of NaHS. Concomitantly, treatment with NaHS alleviated the levels of p38 MAPK and p65 NF-κB phosphorylation but not JNK phosphorylation that occurred in the Aβ(1-40)-injected hippocampus. CONCLUSIONS: These results indicate that NaHS could significantly ameliorate Aβ(1-40)-induced spatial learning and memory impairment, apoptosis, and neuroinflammation at least in part via the inhibition of p38 MAPK and p65 NF-κB activity, suggesting that administration of NaHS could provide a therapeutic approach for AD. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/22898621/Hydrogen_sulfide_attenuates_spatial_memory_impairment_and_hippocampal_neuroinflammation_in_β_amyloid_rat_model_of_Alzheimer's_disease_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-9-202 DB - PRIME DP - Unbound Medicine ER -