NDLI: Anti-Inflammatory Effects of Ladostigil and Its Metabolites in Aged Rat Brain and in Microglial Cells

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Anti-Inflammatory Effects of Ladostigil and Its Metabolites in Aged Rat Brain and in Microglial Cells

Journal of Neuroimmune Pharmacology : Volume 7, Issue 1, Supplement,April 2012

Journal of Neuroimmune Pharmacology : Volume 7, Issue 1, March 2012

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Anti-Inflammatory Effects of Ladostigil and Its Metabolites in Aged Rat Brain and in Microglial Cells

Content Provider	Springer Nature Link
Author	Panarsky, Rony Luques, Lisandro Weinstock, Marta
Copyright Year	2012
Abstract	Impaired mitochondrial function accompanied by microglial activation and the release of nitric oxide (NO) and pro-inflammatory cytokines has been reported in Alzheimer's disease, its prodromal phase of Mild Cognitive Impairment (MCI) and in aged rats. The present study showed that 6 months treatment of 16 month old rats with ladostigil (1 mg/kg/day), a novel drug designed for the treatment of MCI, prevented the development of spatial memory deficits at 22 months of age and significantly decreased the gene expression of IL-1β, IL-6, TNF-α and inducible nitric oxide synthase (iNOS) in the parietal cortex. It was also shown that concentrations ranging from 1nM-1 μM of ladostigil and three of its active metabolites inhibited the release of nitric oxide (NO) induced by lipopolysaccharide (LPS) from mouse microglial cells by up to 35–40 %. Ladostigil and its metabolites (10nM) also reduced TNF-α mRNA and protein by 25–35 % and IL-1β and inducible nitric oxide synthase (iNOS) mRNA by 20–35 %. The concentration of 10nM is in the range of that of the parent drug, R-MCPAI and R-HPAI found in plasma after oral administration of ladostigil (1 mg/kg/day) to rats. All the compounds inhibited the degradation of IkB-α and nuclear translocation of the p65 subunit of NF-kB. They also inhibited phosphorylation of p38 and ERK1/2 mitogen-activated protein kinase (MAPK), but had no effect on that of JNK. We propose that the anti-inflammatory activity may contribute towards the neuroprotective action of ladostigil against the development of memory impairments induced by aging or toxin-induced microglial activation.
Starting Page	488
Ending Page	498
Page Count	11
File Format	PDF
ISSN	15571890
Journal	Journal of Neuroimmune Pharmacology
Volume Number	7
Issue Number	2
e-ISSN	15571904
Language	English
Publisher	Springer US
Publisher Date	2012-03-28
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Aging rats Cytokines Lipopolysaccharide Microglia Mitogen activated protein kinase Nitric oxide Virology Pharmacology/Toxicology Cell Biology Immunology Neurosciences
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Allergy Pharmacology Immunology

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