title: Protective effects of bexarotene against amyloid-β25-35-induced dysfunction in hippocampal neurons through the insulin signaling pathway.
abstract: BACKGROUND
  Bexarotene, a retinoid X receptor agonist, has been shown to reverse neurodegeneration in mouse models of Alzheimer's disease (AD), accompanied by a decreased level of amyloid-β (Aβ), which is a hallmark of AD. However, the mechanism underlying this therapeutic effect may involve enhancing the sensitivity to insulin.
  
  
  OBJECTIVE
  This study was to test the hypothesis that bexarotene would protect against Aβ25-35-induced dysfunction through the insulin signaling pathway.
  
  
  METHODS
  Using a whole-cell patch clamp technique, the excitability and voltage-gated potassium currents of hippocampal neurons were examined in four groups of cells (control, Aβ, Aβ+bexarotene and bexarotene).
  
  
  RESULTS
  It was found that insulin increased the excitability of neurons. Bexarotene could enhance this effect and reverse the Aβ25-35-induced decrease in the firing rate of the action potential (AP). In addition, the properties of the single AP (sAP) and voltage-gated outward K+ currents were recorded, which finally showed similar changes to those in the firing frequency.
  
  
  CONCLUSIONS
  The effects of bexarotene on Aβ-impaired excitability and sAP duration were mainly associated with K+ channels through insulin signaling pathway, which may be an additional mechanism underlying the protective effect of bexarotene on AD.
authors.affiliation: College of Medicine, Nankai University, Tianjin, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Dai
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yang
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000077610:Bexarotene; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D017208:Rats, Wistar; D047488:Retinoid X Receptors / Q000819:agonists; D015398:Signal Transduction; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D051668:Delayed Rectifier Potassium Channels; D007328:Insulin; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; C074636:amyloid beta-protein (25-35); D000077610:Bexarotene