S not seen in the AD brain, tissue levels of inflammatory mediators including cytokines, chemokines, oxygen free radicals and reactive nitrogen species, are altered [5,6]. Numerous reports have indicated that neuro-inflammatory process contributes to the pathogenesis of AD. Study performed in transgenic animals suggest that neuroinflammation plays an important role in the process of cerebral amyloid deposition [7]. It has been shown that inflammatory cytokines such as Interleukin (IL)-1, IL-6, Tumor necrosis factor-gTNF-) or Transforming growth factor- (TGF-) can augment APP expression [8,9] and A formation [10]. It was also reported that cytokines are able to transcriptionally upregulate -secretase mRNA, protein and enzymatic activity [11]. -secretase is a key rate-limiting enzyme that initiates A formation [12]. Without -secretase, A synthesis is either abolished or considerably reduced [13]. Moreover, McGeer and Rogers proposed possible therapeutic effects of anti-inflammatory agents on the patients with AD [14]. Inflammatory mediators present in AD lesions are thought to stimulate underlying key events of the pathological cascade that result in increased A production with recruitment and activation of microglial cells [15]. Many persons with AD die with systemic inflammation such as a lung or bladder infection. The systemic inflammation will lead to the generation of circulating cytokines, which will have in turn an impact on the central nervous system [16]. Furthermore, it was also reported that intraperitoneal injection of lipopolysaccharide (LPS) induces cognitive impairment in mice [17,18]. However, underlying mechanisms involved in LPS induced cognitive impairment are not known. To investigate the impact of systemic inflammation on memory impairment and its role in cortical amyloid formation and deposition, mice were intraperitoneally injected with LPS to generate systemic inflammation, and then investigated for the possi-ble mechanisms of LPS-induced memory impairment and amyloidogenesis in vivo and in vitro.MethodsAnimals Male ICR mice (Damool Science, Korea) weighing 250 g and Sprague-Dawley rats weighing 20000 g, were used in all experiments. Animals were maintained in accordance with the National Institute of Toxicological Research, Korea Food and Drug Administration guidelines for the care and use of laboratory animals.Domvanalimab Animals were housed in two cages (five per cage) and in a 22 2 and 45 65 relative humidity environment under a 12hr light/12-hr dark cycle (8:00 a.Anastrozole m.PMID:23341580 8:00 p.m.). All animals had free access to food (Samyang Foods, Seoul, Korea) and water. The anti-inflammatory sulindac sulfide (3.75 or 7.5 mg/kg) was given orally for 3 weeks prior to the injection of LPS in in vivo study.The mice were randomly divided within each cage and injected intraperitoneally with either 250 g/kg of Lipopolysaccharide (LPS) or sterile saline (0.9 NaCl). For all experiments, LPS (Escherichia coli, serotype 055:B5, Sigma, St. Louis, MO, USA) was used to induce an inflammatory response and was injected once on day 1 of behavioral testing. All injections were administered 4 hrs prior to testing. This allows enough time for the development of neuro-inflammation expressing central IL-1 gene (most notably in circumventricular organs, meningeal tissue, and choroid plexus) at this dose and similar doses of intraperitoneal LPS [19].Behavioral test 1. Passive avoidance test (Step-through test) The passive avoidance test is a widely accepted.
