viewed as the most valid models for understanding cognitive deficits and their neurobiological substrates in the elderly. Grey mouse lemur, Microce- bus murinus, shows age-related changes similar to those of aging humans, and some older mouse lemurs show evidence of Alzheimer’s pathology, e.g. amyloid plaques (Languille et al, 2012). The aim of this study is 1) to identify animals with age-related cognitive deficit, 2) to investigate potential detection of blood biomarkers of neurodegenerative progression. Methods: Young (n¼13), middle-aged (n¼16) and old (n¼12) male mouse lemurs were tested in hang and balance tasks, in open field and plus-maze tests, in spontaneous alternation task, novel object recognition test and in the Barnes maze test. APPholoprotein and the 55kDa-APP-CTF bands were determined from platelets by Western blot in 15 males of different ages. Results: Psychomotor capacities and anxiety-related behaviors decreased abruptly from middle to late adulthood. Mnesic functions were unequally affected with aging. Whereas spontaneous alternation task suggested a pro- gressive and widespread age-related decline of spatial working memory, both spatial reference and novel object recognition memory tasks revealed a large individual variability in the middle-aged and old animals. Hierarchi- cal clustering analysis revealed that episodic-like memory was strongly impaired only in 7 middle-aged/old animals. Biomarkers of disease progres- sion were successfully detected in blood. Results show high inter-individual variability especially around middle-age with no clear relation to cognitive status. Conclusions: These behavioral data offer the opportunity to distin- guish normal and neuropathological aging in this non-human primate model as compared to human aging. Successful determination of blood biomarkers opens perspective for long term follow up and correlative approach of the neurodegenerative progression in a non human primate species. This re- search met ethical requirements of the EC Council Directive (2010/63/ UE) and was part of the PharmaCog consortium. P1-008 MEMANTINE PREVENTS THE REFERENCE AND WORKING MEMORY IMPAIRMENT CAUSED BY SLEEP DEPRIVATION IN OCTODON DEGUS, A POTENTIAL ANIMAL MODEL FOR ALZHEIMER’S DISEASE Ernesto Tarragon Cros 1 , Dolores Lopez 2 , Cristina Estrada 2 , Francisco Ros- Bernal 3 , Jos e Enrique Yuste 3 , Yves Lamberty 4 , Fabien Pifferi 5 , Regis Bordet 6 , Jill Richardson 7 , Trinidad Herrero 2 , 1 Universitat Jaume I, Castellon, Spain; 2 University of Murcia, Murcia, Spain; 3 Universitat Jaume I, Castellon, Spain; 4 UCB Pharma S.A., Brussels, Belgium; 5 UMR Centre National de la Recherche Scientifique, Brunoy, France; 6 Universit e Lille 2, UL2, Lille, France; 7 GlaxoSmithKline R&D China Group, Stevenage, United Kingdom. Contact e-mail: fabien.pifferi@gmail.com Background: Age-related Alzheimer’s disease (AD) is the most common form of dementia and directly affects several cognitive domains crucial for daily functioning, such as attention or memory. Current pharmacother- apy is focused on the improvement of these different symptoms. Within this context, preclinical research using models for the study of age-related disorders is crucial for the development and improvement of pharmacolog- ical strategies. Sleep deprivation (SD) is a validated model to induce tempo- rary cognitive impairment. The O. degus has been recently proposed as a potential preclinical model relevant for neurodegenerative diseases. This rodent presents some advantages over other models including rats and triple-transgenic mice, which make it a promising alternative for such studies. One of the actual compounds registered to treat cognitive symptom- sis memantine. Thus, we therefore studied the effect of memantine on cog- nitive impairment induced by SD in the O. degus. Methods: To this aim, we trained and tested the animals in different behavioral paradigms validated for memory evaluation: the Radial Arm Maze, and the Novel Object Recog- nition test. Before the test, we assigned the animals to a control (CTL, n¼8) or an SD (n¼8) condition. SD was performed following a gentle handling procedure. Animals were treated with vehicle or 10-mg/kg of memantine (IP) before the dark cycle started. Results: Our results showed that meman- tine (10 mg/kg) had no effect on CTL animals while it effectively prevented the cognitive impairment caused by SD in the different cognitive domains evaluated. Conclusions: The positive effect of memantine in counteracting SD in this species further support the potential of both the challenge and the species as a promising model with translational properties, and will enable a better understanding of the behavioral features of memantine’s effects. P1-009 DEVELOPMENT OF AN EXPERIMENTAL MODEL OF INSULIN RESISTANCE–INDUCED ALZHEIMER’S DISEASE Anand Sachdeva 1 , Anurag Kuhad 2 , Kanwaljit Chopra 2 , 1 Panjab University, Chandigarh, India; 2 University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. Contact e-mail: sachdeva83@gmail.com Background: Alzheimer’s disease is one of the most disabling and burden- some health conditions worldwide. Insulin contributes to normal brain func- tioning and peripheral insulin abnormalities increase the risk for memory loss and neurodegenerative disorders such as Alzheimer’s disease. Epidemi- ological studies on cognitive impairment in patients with diabetes found evidence of cross sectional and prospective associations between type 2 diabetes and moderate degree of cognitive impairment, both for memory and executive functions. Several studies suggest that consumption of a fat rich diet leads to peripheral insulin resistance and impede cognitive perfor- mance. Insulin resistance is associated with an increase in circulating advanced glycosylation end products (AGEs) and the increased expression of the receptor for AGEs (RAGE). Fructose has been reported as a potent agent in forming AGEs and, thus, may play a significant role in the develop- ment cognitive function. Thus, the present study was designed to develop fructose-induced insulin resistance associated Alzheimer’s disease and fur- ther to elucidate the possible neurogenic relationship between two clinical entities. Methods: Six-week-old male Wistar rats were fed with 15% fruc- tose in drinking water for 24 weeks. Body mass, food and water intake were measured regularly. Insulin resistance associated cognitive impairment was measured by using Morris water maze test (computer tracking using EthoVision software) and elevated plus maze on 14th, 16th, 20th, 22nd and 24th weeks. At the end of study, animals were sacrificed for estimating biochemical and molecular parameters. Results: Insulin resistance was evident at 6th week and persisted till end of study (24th week) as demon- strated by significantincrease in body weight, plasma insulin levels, blood glucose levels, glycosylated heamoglobin levels,HOMA-IRlevelsand deranged lipid profile.Cognitive deficit was significantly evident at 20th, 22nd and 24th weeks. This time-dependent study suggested emergence of insulin resistance-induced memory impairment after 20th weeks of fructose consumption. Fructose-induced neuronal deficits were coupled with signif- icant alterations in oxidative-nitrodative stress, inflammatory cytokines (TNF-a, TGF-b) and growth factors (NGF levels). Conclusions: These find- ings indicate that chronic fructose consumption generated a condition of- neuronal insulin resistance. Impairment in neuronal insulin response Sunday, July 14, 2013: Poster Presentations: P1 P156