Neuroendocrine immunomodulation network dysfunction in SAMP8 mice and PrP-hAβPPswe/PS1ΔE9 mice: potential mechanism underlying cognitive impairment

// Jian-hui Wang 1,2,* , Xiao-rui Cheng 1,2,* , Xiao-rui Zhang 1,2 , Tong-xing Wang 1,2 , Wen-jian Xu 3 , Fei Li 3 , Feng Liu 1,2 , Jun-ping Cheng 1,2 , Xiao-chen Bo 3 , Sheng-qi Wang 3 , Wen-xia Zhou 1,2 and Yong-xiang Zhang 1,2 1 Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China 2 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China 3 Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China * These authors contributed equally to this work and as co-first authors Correspondence to: Xiao-rui Cheng, email: // Wen-xia Zhou, email: // Yong-xiang Zhang, email: // Keywords : Alzheimer's disease, neuroendocrine immunomodulation, Senescence-accelerated mouse prone 8 strain (SAMP8), PrPhAβPPswe/PS1ΔE9 (APP/PS1) mice, learning and memory, Gerotarget Received : February 14, 2016 Accepted : March 18, 2016 Published : March 28, 2016 Abstract Senescence-accelerated mouse prone 8 strain (SAMP8) and PrP-hAβPPswe/PS1 ΔE9 (APP/PS1) mice are classic animal models of sporadic Alzheimer’s disease and familial AD respectively. Our study showed that object recognition memory, spatial learning and memory, active and passive avoidance were deteriorated and neuroendocrine immunomodulation (NIM) network was imbalance in SAMP8 and APP/PS1 mice. SAMP8 and APP/PS1 mice had their own specific phenotype of cognition, neuroendocrine, immune and NIM molecular network. The endocrine hormone corticosterone, luteinizing hormone and follicle-stimulating hormone, chemotactic factor monocyte chemotactic protein-1, macrophage inflammatory protein-1β, regulated upon activation normal T cell expressed and secreted factor and eotaxin, pro-inflammatory factor interleukin-23, and the Th1 cell acting as cell immunity accounted for cognitive deficiencies in SAMP8 mice, while adrenocorticotropic hormone and gonadotropin-releasing hormone, colony stimulating factor granulocyte colony stimulating factor, and Th2 cell acting as humoral immunity in APP/PS1 mice. On the pathway level, chemokine signaling and T cell receptor signaling pathway played the key role in cognition impairments of two models, while cytokine-cytokine receptor interaction and natural killer cell mediated cytotoxicity were more important in cognitive deterioration of SAMP8 mice than APP/PS1 mice. This mechanisms of NIM network underlying cognitive impairment is significant for further understanding the pathogenesis of AD and can provide useful information for development of AD therapeutic drug.