Hesperidin ameliorates behavioral impairments and neuropathology of transgenic APP/PS1 mice

Behav Brain Res. 2015 Mar 15:281:32-42. doi: 10.1016/j.bbr.2014.12.012. Epub 2014 Dec 12.

Abstract

In addition to cognitive impairments, deficits in non-cognitive behaviors are also common neurological sequelae in Alzheimer's disease and its animal models. Hesperidin, a flavanone glycoside found abundantly in citrus fruits, was orally given (100 mg/kg body weight) to 5-month-old transgenic APP/PS1 mice, a mouse model of cerebral amyloidosis for Alzheimer's disease. After a relatively short-term treatment of 10 days, hesperidin significantly restored deficits in non-cognitive nesting ability and social interaction. Further immunohistochemical analysis showed significantly attenuated β-amyloid deposition, plaque associated APP expression, microglial activation and TGF-β immunoreactivity in brains of APP/PS1 mice, which suggests that ameliorated behavioral impairments might be attributable to reduced Aβ deposition and attenuated neuro-inflammatory reaction. Additionally, efficient anti-inflammatory effects of hesperidin were confirmed in vitro. Our findings suggest that hesperidin might be a potential candidate for the treatment of AD or even other neurodegenerative diseases.

Keywords: Alzheimer's disease; Behavioral deficit; Cerebral amyloidosis; Hesperidin; Neuro-inflammation; Transgenic mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Amyloid beta-Protein Precursor / deficiency
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Brain / drug effects
  • Brain / pathology*
  • Disease Models, Animal
  • Hesperidin / pharmacology*
  • Male
  • Mice
  • Mice, Transgenic
  • Microglia / drug effects
  • Microglia / immunology
  • Plaque, Amyloid / drug therapy
  • Presenilin-1 / deficiency
  • Presenilin-1 / genetics
  • Psychomotor Performance / drug effects*
  • Social Behavior*
  • Transforming Growth Factor beta / immunology
  • Treatment Outcome

Substances

  • Amyloid beta-Protein Precursor
  • Presenilin-1
  • Transforming Growth Factor beta
  • Hesperidin