title: Trans-cinnamaldehyde improves memory impairment by blocking microglial activation through the destabilization of iNOS mRNA in mice challenged with lipopolysaccharide.
abstract: Microglia activation and neuroinflammation are critically involved in pathogenesis of neurodegenerative disorders. Patients with neurodegenerative disorders often suffer memory impairment and currently there is no effective treatment for inflammation-led memory impairment. Trans-cinnamaldehyde (TCA) isolated from medicinal herb Cinnamomum cassia has been shown to exhibit anti-inflammatory capability. However, the potential of TCA to be used to improve memory impairment under neuroinflammation has not been explored. Primary microglia stimulated by lipopolysaccharide (LPS) were used to evaluate the potential anti-neuroinflammatory effects of TCA by examining the production of nitric oxide (NO), expression of inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines, and activation of MAPKs. A mouse model of LPS-induced memory impairment was established to assess the neuroprotective effects of TCA against memory deficit and synaptic plasticity inhibition by both behavioral tests and electrophysiological recordings. TCA pretreatment decreased LPS-induced morphological changes, NO production and IL-1β release in primary microglia. Decreased NO production was due to the accelerated degradation of iNOS mRNA in LPS-stimulated microglia through TCA's inhibitory effect on MEK1/2-ERK1/2 signaling pathway. TCA was able to reduce the levels of iNOS and phosphorylated ERK1/2 in hippocampus of mice challenged with LPS. Most importantly, TCA significantly lessened memory deficit and improved synaptic plasticity in LPS-challenged mice. This study demonstrates that TCA suppressed microglial activation by destabilizing iNOS mRNA, which leads to improved memory impairment in mice suffering neuroinflammation.
authors.affiliation: Department of Physiology, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physiology, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Zhangang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Physiology, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Physiology, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Zhenxia
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, 232 Waihuandong Road, Guangzhou 510006, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China. Electronic address: ying6122003@aliyun.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex; D004195:Disease Models, Animal; D004795:Enzyme Stability / Q000187:drug effects; D004926:Escherichia coli; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018697:Nootropic Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D012333:RNA, Messenger; D009569:Nitric Oxide; D000171:Acrolein; D052247:Nitric Oxide Synthase Type II; C012843:cinnamaldehyde
keywords: MEK1/2-ERK1/2 signaling pathway; Memory impairment; Microglial activation; Neuroinflammation; Trans-cinnamaldehyde; iNOS mRNA stability