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P1‐418: SUSTAINED DELIVERY OF SURFACE MODIFIED DONEPEZIL HCL LOADED PCL NANOPARTICLES FOR ALZHEIMER'S DISEASE
Author(s) -
Amirthalingam Muthukumar,
Nayanabhirama Udupa,
Mutalik Srinivas
Publication year - 2014
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.2014.05.661
Subject(s) - zeta potential , nanoparticle , acetylcholinesterase , nanotoxicology , chemistry , donepezil , biophysics , pharmacology , chromatography , materials science , nanotechnology , biochemistry , enzyme , medicine , dementia , disease , pathology , biology
pathways. Since brain inflammation and hippocampal neurogenesis may correlate with bioenergetic function, we also analyzed genes and proteins that reflect neurogenesis and brain inflammation activity. Results: 21month old C57BL/6 mice showed increased brain PGC-1a protein, mTOR and phospho-mTOR protein, citrate synthase mRNA, and mtDNA copy number. Hippocampal VEGF-A gene expression trended higher, and a positive correlation between VEGF-A and PRC mRNA levels was observed. Brain DCX, BDNF, TNF-a, and CCL11 gene expression, as well as plasma CCL11 protein levels, were unchanged. Despite these apparent negative findings, a negative correlation between plasma CCL11 protein levels and hippocampal DCX gene expression was observed; further analysis indicated exercise may mitigate this relationship. Conclusions: Supra-lactate threshold exercise beneficially impacts bioenergetic-relevant parameters in the brains of aged mice. Our data further suggest supra-lactate threshold exercise may enhance neurogenesis by uncoupling it from the effects of inflammatory chemokines. This study supports the view that exercising above the lactate threshold may benefit the aging brain.