(Number 4E,F). Open in a separate window Open in a separate window Topotecan Figure 4 HE-A and HE-S reduce glial activation in APP/PS1 mice. mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the jobs including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce c-COT AD pathology via reducing amyloid deposition and advertising neurogenesis, erinacine A can also inhibit amyloid production and is worth to be further developed for AD restorative use. is an edible and medicinal mushroom with numerous pharmacological activities, including anti-neurodegenerative and neuroprotective activities [11,12]. Erinacines isolated from its mycelia have been known to possess a potent stimulating effect on nerve growth factor (NGF) manifestation and secretion [13]. Recent studies have shown that fruiting body ameliorated A-induced cognitive declined in mice and people with slight cognitive impairment [14,15]. Our earlier studies also shown that mycelium ameliorated A-induced cognitive decrease in mice [16]. The major components of mycelium are erinacine A (HE-A), C (HE-C), and S (HE-S) which are belong to cyanthin diterpenoid (both HE-A and HE-C) and sesterterpene (HE-S). For verifying the effect of these different constituents of mycelium on AD-related pathologies, HE-A and HE-S were isolated and their effects were compared in the present study. The APPswe/PS1dE9 mouse model (APP/PS1), co-expressed Swedish, mutated human being APP695 and human being mutated presenilin 1 (PS1) in which exon 9 is definitely deleted [17], show AD-like pathological and behavioral changes, including build up of amyloid plaques in mind, degeneration of cholinergic system, and impaired exploratory behavior and spatial memory space [18]. Improved A production and plaque formation in APP/PS1 mice offers been shown to occur as early as 3 to 5 5 months-old [19], and impaired spatial learning and memory space was observed at six months-old [20,21]. Furthermore, the neurogenesis is also found to be impaired in the APP/PS1 mouse at 3 to 6 months-old [22]. In the present study, the potentials of HE-A and HE-S on amyloid pathology in 5 weeks aged APP/PS1 mice were investigated and compared. Our data suggests that although both HE-A and HE-S were active on reducing A plaque growth, diminishing neuroinflammation and increasing the level of insulin-degrading enzyme (IDE), only HE-A reduced the level of insoluble amyloid and APP C-terminal fragment (CTF) and decreased the initiation of A formation. 2. Results 2.1. Experimental Design APP/PS1 transgenic mice was used as AD animal model to examine the effects of HE-A and HE-S (Number 1A) on ameliorating AD-related pathologies. For studying the therapeutic effect in short-term administration, woman APP/PS1 mice were administrated by gavage with vehicle (= 8), HE-A or HE-S (30 mgkg?1day?1, = 8 for each group) at 5 months of age for 30 days. For control, Topotecan woman Wild type mice (WT) were administrated by gavage with vehicle (= 5) at 5 weeks of age for 30 days. Male mice were also used to verify the difference between male and woman, and no significant difference was observed. BrdU (5-bromo-2-deoxyuridine) was Topotecan injected intraperitoneally at 50 mgkg?1day?1 during the last 7 days. The fine detail A-related pathological changes in mice mind were examined using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and immunoblotting (Number 1B). For behavior effect assays, the experiment is designed to the long-term administration of vehicle (= 8) or HE-A (10 or 30 mgkg?1day?1, = 8) to APP/PS1 mice at 5 months of age for 100 days (Number 1C). For control, woman Wild type mice (WT) were administrated by gavage with vehicle (= 5) at 5 weeks of age for 100 days. Open in a separate window Number 1 The structure of erinacine A (HE-A) and erinacine S (HE-S) and experimental design. (A) The structure of HE-A and HE-S were demonstrated; (B) Short-term administration: Five month aged woman amyloid precursor protein (APP)/human being mutated presenilin 1 (PS1) mice were orally given with vehicle, HE-A and HE-S for 30 days (= 8 for each group). BrdU was injected intraperitoneally in the last 7 days of drug administration for detecting neurogenesis. The mice were scarified and the indicated assays were performed; (C) Long-term administration: Five weeks aged APP/PS1 mice were orally given with vehicle or HE-A for 100 days (= 8 for each group). The jobs of burrowing, nesting, and Morris water maze (MWM) were initiated at 70th, 80th, and 90th day time after orally administration, respectively. Burrowing task was performed during the time between the 70th and 79th day time after drug administration; nesting task was performed during the time between.