Daidzein augments cholesterol homeostasis via apoE to promote functional recovery in chronic stroke

Eunhee Kim, Moon Sook Woo, Luye Qin, Thong Ma, Cesar D. Beltran, Yi Bao, Jason A. Bailey, Dale Corbett, Rajiv R. Ratan, Debomoy Lahiri, Sunghee Cho

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Stroke is the world’s leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, is a clinically approved agent that has a neuroprotective effect in vitro, and it promotes axon growth in an animal model of optic nerve crush. The current study investigates the efficacy of daidzein on neuroprotection and functional recovery in a clinically relevant mouse model of stroke recovery. In light of the fact that cholesterols are essential lipid substrates in injury-induced synaptic remodeling, we found that daidzein enhanced the cholesterol homeostasis genetic program, including Lxr and downstream transporters, Apoe, Abca1, and Abcg1 genes in vitro. Daidzein also elevated the cholesterol homeostasis genes in the poststroke brain with Apoe, the highest expressing transporter, but did not affect infarct volume or hemispheric swelling. Despite the absence of neuroprotection, daidzein improved motor/gait function in chronic stroke and elevated synaptophysin expression. However, the daidzein-enhanced functional benefits and synaptophysin expression were abolished in Apoe-knock-out mice, suggesting the importance of daidzein-induced ApoE upregulation in fostering stroke recovery. Dissociation between daidzein-induced functional benefits and the absence of neuroprotection further suggest the presence of nonoverlapping mechanisms underlying recovery processes versus acute pathology. With its known safety in humans, early and chronic use of daidzein aimed at augmenting ApoE may serve as a novel, translatable strategy to promote functional recovery in stroke patients without adverse acute effect.

Original languageEnglish (US)
Pages (from-to)15113-15126
Number of pages14
JournalJournal of Neuroscience
Volume35
Issue number45
DOIs
StatePublished - Nov 11 2015

Fingerprint

Apolipoproteins E
Homeostasis
Stroke
Cholesterol
Synaptophysin
Nerve Crush
daidzein
Isoflavones
Foster Home Care
Neuroprotective Agents
Optic Nerve
Hypercholesterolemia
Gait
Knockout Mice
Genes
Axons
Up-Regulation
Animal Models
Pathology
Lipids

Keywords

  • ApoE
  • Cholesterol transporter
  • Daidzein
  • Motor/gait function
  • Stroke recovery

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Daidzein augments cholesterol homeostasis via apoE to promote functional recovery in chronic stroke. / Kim, Eunhee; Woo, Moon Sook; Qin, Luye; Ma, Thong; Beltran, Cesar D.; Bao, Yi; Bailey, Jason A.; Corbett, Dale; Ratan, Rajiv R.; Lahiri, Debomoy; Cho, Sunghee.

In: Journal of Neuroscience, Vol. 35, No. 45, 11.11.2015, p. 15113-15126.

Research output: Contribution to journalArticle

Kim, E, Woo, MS, Qin, L, Ma, T, Beltran, CD, Bao, Y, Bailey, JA, Corbett, D, Ratan, RR, Lahiri, D & Cho, S 2015, 'Daidzein augments cholesterol homeostasis via apoE to promote functional recovery in chronic stroke', Journal of Neuroscience, vol. 35, no. 45, pp. 15113-15126. https://doi.org/10.1523/JNEUROSCI.2890-15.2015
Kim, Eunhee ; Woo, Moon Sook ; Qin, Luye ; Ma, Thong ; Beltran, Cesar D. ; Bao, Yi ; Bailey, Jason A. ; Corbett, Dale ; Ratan, Rajiv R. ; Lahiri, Debomoy ; Cho, Sunghee. / Daidzein augments cholesterol homeostasis via apoE to promote functional recovery in chronic stroke. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 45. pp. 15113-15126.
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