Subchronic administration of ascorbic acid elicits antidepressant-like effect and modulates cell survival signaling pathways in mice

J Nutr Biochem. 2016 Dec:38:50-56. doi: 10.1016/j.jnutbio.2016.09.004. Epub 2016 Sep 14.

Abstract

In this study, we examined the ability of subchronic ascorbic acid administration to produce an antidepressant-like effect in the mouse tail suspension test (TST). Moreover, we investigated the effect of this vitamin on hippocampal and cerebrocortical brain-derived neurotrophic factor (BDNF) immunocontent, phosphorylation of protein kinase B (AKT), extracellular signal-regulated kinase (ERK), p38MAPK and c-Jun. N-terminal kinase (JNK). Fluoxetine (10 mg/kg, positive control, po) or ascorbic acid (0.1 and 1 mg/kg, po), administered once daily for 21 days, produced a significant antidepressant-like effect in the TST. The significant effects obtained in protein immunocontents were: administration of ascorbic acid at 1 mg/kg induced an increase in AKT phosphorylation in cerebral cortex of mice. Ascorbic acid treatment (1 mg/kg), similar to fluoxetine, decreased hippocampal p38MAPK but did not alter ERK or JNK phosphorylation. These results extend the data about the antidepressant-like effect of ascorbic acid by exploring, for the first time, the intracellular pathways involved in its antidepressant properties after subchronic administration.

Keywords: AKT; Antidepressant; Ascorbic acid; Tail suspension test; p38(MAPK).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / therapeutic use*
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / therapeutic use*
  • Cell Survival / drug effects
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Depression / diet therapy*
  • Depression / drug therapy
  • Depression / metabolism
  • Dietary Supplements*
  • Enzyme Activation / drug effects
  • Female
  • Fluoxetine / therapeutic use
  • Hindlimb Suspension
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Mice
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Proteins c-akt / agonists*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antidepressive Agents
  • Antioxidants
  • Nerve Tissue Proteins
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Akt1 protein, rat
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases
  • Ascorbic Acid