Nasal obstruction during adolescence induces memory/learning impairments associated with BDNF/TrkB signaling pathway hypofunction and high corticosterone levels

J Neurosci Res. 2018 Jun;96(6):1056-1065. doi: 10.1002/jnr.24216. Epub 2018 Feb 2.

Abstract

The hippocampus is an important brain region involved in memory and learning. Brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), and phospho-p44/p42 mitogen-activated protein kinase (MAPK) are known to contribute to hippocampal memory/learning. The present study aimed to clarify the effects of nasal obstruction during the growth period on memory/learning in an animal model, using combined behavioral, biochemical, and histological approaches. Male BALB/C mice underwent unilateral nasal obstruction (UNO) by cauterization at 8 days of age and were subjected to Y-maze and passive avoidance tests at 15 weeks of age. The serum corticosterone levels were measured using an enzyme-linked immunosorbent assay, and brain tissues were subjected to hematoxylin-eosin staining and histological analysis or homogenization and Western blot analysis. Compared with control mice, UNO mice had lower blood oxygen saturation levels and exhibited apparent memory/learning impairments during behavioral testing. Additionally, the UNO group had higher hippocampal BDNF levels and serum corticosterone levels, lower hippocampal TrkB and phospho-p44/p42 MAPK levels, and reduced neuron numbers relative to controls. Our findings suggest that UNO during adolescence affects the hippocampus and causes memory/learning impairments.

Keywords: BDNF; SpO2; corticosterone; hippocampus; memory/learning impairment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning
  • Body Weight
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Corticosterone / blood*
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Learning Disabilities / metabolism*
  • Learning Disabilities / pathology
  • Male
  • Maze Learning
  • Membrane Glycoproteins / metabolism*
  • Memory / physiology*
  • Memory Disorders / metabolism*
  • Memory Disorders / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • Nasal Obstruction / blood
  • Nasal Obstruction / metabolism*
  • Nasal Obstruction / pathology
  • Nasal Obstruction / psychology
  • Protein-Tyrosine Kinases / metabolism*
  • Random Allocation
  • Signal Transduction

Substances

  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases
  • Mitogen-Activated Protein Kinases
  • Corticosterone