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P4–421: Effects of small anionic sulfates and sulfonates on amyloid–beta/heparan sulfate proteoglycan (HSPG) interaction in an in vitro model of amyloid deposition
Author(s) -
Husemann Jens,
Frahlich Thomas,
Anankov Roman,
Hossein Ruhella,
Silverstein Samuel
Publication year - 2006
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.2006.05.2163
Subject(s) - chemistry , amyloid (mycology) , heparan sulfate , in vitro , proteoglycan , perlecan , biochemistry , in vivo , biophysics , microbiology and biotechnology , glycosaminoglycan , extracellular matrix , biology , inorganic chemistry
cannabinoid receptor agonist, WIN-55212-2, on microglia activation induced by a chronic intracerebroventricular lipopolysaccharide (LPS) infusion and its possible mechanisms of action. Methods: Daily injections of WIN-55212-2 (0.5 or 1.0 mg/kg, i.p.) were given to three months old male rats implanted into the 4 ventricle with a chronic indwelling cannula connected to an osmotic minipump containing LPS (250 ng/hr) or vehicle. During the third week of treatment, the rats were behaviorally tested using the Morris water pool task. Results: Animals treated with WIN demonstrated a significant anti-inflammatory effect represented by a reduction in microglia activation. LPS-infused rats treated with WIN-55212-2 did not demonstrate impaired performance in the Morris water pool task as compared to the LPS-infused rats without WIN-55212-2. We are currently investigating the endocannabinoid receptor subtype that is responsible for this anti-inflammatory action and whether specific regions of the brain are more vulnerable to the consequences of the inflammation. Conclusions: These results highlight the potential benefits of pharmacological manipulation of endocannabinoid receptor within the brain and may guide the design of more effective therapies for AD.