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[P3–040]: PDE9 INHIBITION IMPROVES COGNITION IN MICE BY A MECHANISM DIFFERENT FROM THE ACETYLCHOLINE ESTERASE INHIBITOR DONEPEZIL
Author(s) -
Rosenbrock Holger,
Giovannini Riccardo,
Fuchs Klaus,
DornerCiossek Cornelia
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1853
Subject(s) - synaptic plasticity , hippocampus , neuroscience , donepezil , prefrontal cortex , spontaneous alternation , nmda receptor , psychology , striatum , working memory , morris water navigation task , physostigmine , acetylcholine , cognition , cholinergic , pharmacology , chemistry , biology , receptor , medicine , dopamine , biochemistry , dementia , disease
Selaginella delicatula a pteridophyte (popularly known as Sanjeevani) is reported to contain characteristic biflavonoids (amentoflavone) with various biological activities in vitro. In this study, we have tested the hypothesis whether Selaginella flavonoids (SF) possess the potential to abrogate the lipopolysaccharide (LPS)induced biochemical and phenotypic alterations in Drosophila and mice models. Methods: First regimen, mice provided prophylaxis with (SF, 25 & 50mg/kg/d, p.o., for 15d, n1⁄46) were challenged with LPS (0.5mg/kg/d, ip, last 5 days). Phenotypic manifestations were assessed by employing a battery of behavioral assays for dementia (elevated plus maze, Y-maze, Morris water maze, passive avoidance). Hippocampus region was subjected to biochemical assessments viz., mitochondrial dysfunction, oxidative stress and AChE activity. Second regimen, adult Drosophila (n1⁄425, 6 replicates) maintained on SF enriched diet (0.05-0.1%, 7 days), were challenged with LPS (200mg, filter discs) and subsequently subjected to behavioral and biochemical tests. Results:LPS exposure induced significant behavioral aberrations among mice as evident from mazes. The passive avoidance score was markedly reduced among the LPS mice indicating severe dementia traits. Interestingly, the extent of LPS-induced behavioral anomalies among mice given SF prophylaxis was significantly attenuated. Additionally SF mice exhibited reduced oxidative stress markers, nitric oxide levels, diminished AChE activity and improved mitochondrial membrane permeability. In the Drosophila we could reproduce the protective effects of SF prophylaxis as evidenced by diminished LPS-induced general aggressive behavior, oxidative markers and AChE activity. Conclusions:These in vivo data are suggestive of potent neuro-attenuatory propensity of Selaginella flavonoids against LPS-induced dementia in mice and Drosophila and merit further mechanistic investigations.