Premium
P1‐158: PREVENTION OF NEURON FROM TOXICITY INDUCED BY Aβ42 BY P3‐ALCβ PEPTIDES AND THEIR PHARMACOKINETICS IN MICE
Author(s) -
Saito Haruka,
Hata Saori,
Suzuki Toshiharu
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.713
Subject(s) - peptide , toxicity , amino acid , viability assay , in vivo , pharmacokinetics , chemistry , pharmacology , in vitro , biochemistry , hippocampal formation , biology , endocrinology , microbiology and biotechnology , organic chemistry
estrogen loss plays in exacerbating the pathological features of AD are unknown. Methods: Female C57BL6/J mice received either bilateral ovariectomy, to simulate estrogen loss, (OVX; n1⁄420) or SHAM surgery (n1⁄420) at 26 weeks of age. To induce peripheral glucose intolerance and obesity, mice were placed on either a low or high fat diet for 10 weeks. Prefrontal cortex tissue was then isolated and protein content of amyloidogenic markers (sAPPa and sAPPb) and Ab degradation (IDE) were examined. Results: To confirm estrogen loss, OVX mice had reduced uterine weight (p<0.05). In addition, both OVX and HFD led to impairments in glucose tolerance, with the combination having the greatest impairment (p<0.05). HFDmice also had increased terminal body weight (g) (p<0.05), with both OVX and HFD having elevated gonadal white adipose tissue (g) (p<0.05). OVX led to increased sAPPb (p<0.05), and a trending decrease in sAPPa (p<0.10), indicative of APP being processed towards the amyloidogenic cascade. Furthermore, the high fat diet, in combination with a loss of estrogen, led to decreases in IDE protein content (p<0.05). There were no changes however, in BACE1 content (p>0.05). Conclusions: Data from this study provides evidence of a synergistic effect of obesity and estrogen loss reducing mechanisms of Ab degradation. Furthermore, findings indicate how the loss of estrogen promotes the formation of APP cleavage products in the prefrontal cortex. These results contribute to our mechanistic understanding of both the loss of estrogen and nutrition on overall female brain health in relation to AD progression.