Effect of photoperiodic alterations on depression-like behavior and the brain serotonin system in mice genetically different in tryptophan hydroxylase 2 activity

Neurosci Lett. 2019 Apr 23:699:91-96. doi: 10.1016/j.neulet.2019.01.041. Epub 2019 Jan 24.

Abstract

Reduction of natural illumination in fall/winter months causes seasonal affective disorders (SAD) in vulnerable individuals. Neurotransmitter serotonin (5-HT) is involved in the mechanism of SAD. Tryptophan hydroxylase-2 (TPH2) is the key enzyme of 5-HT synthesis in the brain. C1473 G polymorphism in the Tph2 gene is a key factor defining the enzyme activity in the mouse brain. The main aims of the study were to investigate the effects of C1473 G polymorphism on behavior and brain 5-HT system responses to photoperiod alterations. The experiment was carried out on adult mouse males of B6-1473C and B6-1473 G congenic lines with normal and low TPH2 activities, respectively. B6-1473C and B6-1473 G mice were divided into four groups of 8 each and exposed for 28 days to standard-day (14 h light and 10 h darkness) or short-day (4 h light and 20 h darkness) conditions. No effect of photoperiod on locomotor, exploratory activities and anxiety in the open field test was observed. At the same time, photoperiod alterations affected depressive-like immobility in the forced swim test, the 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) levels, 5-HIAA/5-HT ratio and the Htr2a mRNA level in hippocampus and midbrain. The effect of the interaction between C1473 G polymorphism and photoperiod on 5-HT level and 5-HIAA/5-HT ratio in hippocampus was revealed. Short-day conditions reduced the level and increased 5-HIAA/5-HT ratio in this structure only in B6-1473 G mice. At the same time, C1473 G polymorphism does not alter effects of short-day conditions on immobility time in the forced swim test and the Htr2a mRNA level in the brain.

Keywords: 5-HT system; Behavior; C1473G polymorphism; Mice; Photoperiod; Tryptophan hydroxylase 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Depression / genetics
  • Depression / physiopathology*
  • Exploratory Behavior / physiology
  • Hippocampus / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Immobility Response, Tonic / physiology
  • Male
  • Mesencephalon / metabolism
  • Mice
  • Motor Activity / physiology
  • Photoperiod*
  • Polymorphism, Single Nucleotide
  • Receptor, Serotonin, 5-HT2A / biosynthesis
  • Serotonin / metabolism*
  • Tryptophan Hydroxylase / genetics*
  • Tryptophan Hydroxylase / metabolism

Substances

  • Htr2a protein, mouse
  • Receptor, Serotonin, 5-HT2A
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Tph2 protein, mouse
  • Tryptophan Hydroxylase