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P4–014: Allopregnanolone as a regenerative therapeutic for Alzheimer's disease, 4: Impact on neuronal versus gliosis phenotypic differentiation
Author(s) -
Chen Shuhua,
Yao Jia,
Wong Karren,
Brinton Roberta
Publication year - 2013
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.2013.05.1402
Subject(s) - neurogenesis , gliosis , neural stem cell , embryonic stem cell , biology , progenitor cell , immunolabeling , neurosphere , cellular differentiation , in vivo , microbiology and biotechnology , stem cell , pathology , immunology , neuroscience , adult stem cell , medicine , immunohistochemistry , biochemistry , gene
weeks and then subcutaneously injected with vehicle, Allo (10mg/kg), or 17b-estradiol (E2, 60mg/kg). 24 hours after treatment, mice were sacrificed and brain mitochondria were isolated for mitochondrial respiration and bioenergetic enzyme measurements. Results: Adult NSCs from both nonTg and 3xTgAD mice exhibited a significant age-dependent decline in mitochondrial bioenergetic capacity. Further, aNSC derived from 3xTgAD mice at 6 and 18 months exhibited elevated proton leak. In vitro Allo treatment potentiated mitochondrial respiration in both NSCs, neurons and mixed glia. Further, in vivo Allo treatment restored the OVX-induced decrease in mitochondrial respiration in both nonTg and 3xTgAD mice. Allo treatment increased activity of bioenergetic enzymes such as PDH and aKGDH, and suppressed the OVX-induced increase in lipid peroxidation.Conclusions: There was an ageand Alzheimer’s associated decline in mitochondrial function in aNSCs. Allo treatment potentiated mitochondrial function both in vitro and in vivo. Collectively, these data provided mechanistic basis for developing Allo as a multi-tropic AD therapeutics to sustain and enhance mitochondrial function and to promote neurogenic capacity.