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

Abstract

Senescence-accelerated mouse prone 8 strain (SAMP8) and PrP-hAβPPswe/PS1ΔE9 (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.

A young testicular microenvironment protects Leydig cells against age‐related dysfunction in a mouse model of premature aging

“…In other rodent models of premature aging, including the senescence accelerated SAMP8 mouse line (97–99) and premature aging induced by d -galactose administration (100, 101), primary testicular dysfunction is associated with increased testicular ROS production. Studies by Wiley et al (30) demonstrated that CISD2-loss results in a pro-oxidative intracellular environment, which may explain the reduction in testosterone observed in CISD2-KO mice.…”

“…In addition to reduced expression and activity of proteins required for the conversion of cholesterol to testosterone, damage to steroidogenic machinery as a result of perturbation in the balance between the generation of reactive oxygen species (ROS), and their neutralization by antioxidants, is hypothesized to underlie the decreased testosterone production by aged LCs (21,23,24,94,96). In other rodent models of premature aging, including the senescence accelerated SAMP8 mouse line (97)(98)(99) and premature aging induced by D-galactose administration (100, 101), primary testicular dysfunction is associated with increased testicular ROS production. Studies by Wiley et al (30) demonstrated that CISD2-loss results in a pro-oxidative intracellular environment, which may explain the reduction in testosterone observed in CISD2-KO mice.…”

LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAβPPswe/PS1ΔE9 transgenic mice

“…Previously, we found that the NIM network is altered and dysfunctional in a PrP-hAβPPswe/PS1 ΔE9 (APP/PS1) mouse model of familial AD and early-onset AD [29, 30]. In the present study, we examined the effects of long-term oral administration of a novel Liuwei Dihuang formula (LW-AFC) on cognitive impairment, Aβ deposition, and neuronal loss in APP/PS1 mice.…”

MicroRNA-139 modulates Alzheimer’s-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2

“…2 People's Hospital Animal Ethics Committee. The hippocampal injections were performed as described previously (Wang et al, 2016). Briefly, 6-month-old mice received injection of 3 mM miRNA mimics (Genephama, Shanghai, China) into the dentate gyrus by use of a dental drill every week.…”

“…Here, we chose the senescence accelerated mouse prone 8 (SAMP8) strain as an AD mouse model and the senescence-accelerated mouse-resistant 1 (SAMR1) strain as a control (Wang et al, 2016) strain. First, we measured the expression of miR-139 in the SAMP8 (AD model group) and SAMR1 mice (control group).…”