Total and mitochondrial nitrosative stress, decreased brain-derived neurotrophic factor (BDNF) levels and glutamate uptake, and evidence of endoplasmic reticulum stress in the hippocampus of vitamin A-treated rats.

Abstract

Vitamin A supplementation has caused concern among public health researchers due to its ability in decreasing life quality from acute toxicological effects to increasing mortality rates among vitamin supplement users. For example, it was described cognitive decline (i.e. irritability, anxiety, and depression) in patients subjected to long-term vitamin A therapy, as occurs in cancer treatment. However, the mechanism by which vitamin A affects mammalian cognition is not completely understood. Then, we performed the present work to investigate the effects of vitamin A supplementation at clinical doses (1,000-9,000 IU/kg day(-1)) for 28 days on rat hippocampal nitrosative stress levels (both total and mitochondrial), bioenergetics states, brain-derived neurotrophic factor (BDNF), alpha- and beta-synucleins, BiP and dopamine receptor 2 (D2 receptor) contents, and glutamate uptake. We observed mitochondrial impairment regarding respiratory chain function: increased complex I-III, but decreased complex IV enzyme activity. Also, decreased BDNF levels were observed in vitamin A-treated rats. The present data demonstrates, at least in part, that mitochondrial dysfunction and decreased BDNF and D2 receptors levels, as well as decreased glutamate uptake may take an important role in the mechanism behind the previously reported cognitive disturbances associated to vitamin A supplementation.

• Authors: Marcos Roberto de Oliveira, Ricardo Fagundes da Rocha, Laura Stertz, Gabriel Rodrigo Fries, Diogo Losch de Oliveira, Flávio Kapczinski, José Cláudio Fonseca Moreira
• Journal: Neurochemical research (Neurochem Res) Vol. 36 Issue 3 Pg. 506-17 (Mar 2011) ISSN: 1573-6903 [Electronic] United States
• PMID: 21188516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Bax-inhibiting peptide, BIP
• Brain-Derived Neurotrophic Factor
• Oligopeptides
• Peptide Fragments
• Reactive Nitrogen Species
• Receptor for Advanced Glycation End Products
• Receptors, Dopamine D2
• Receptors, Immunologic
• Vitamins
• alpha-Synuclein
• amyloid beta-protein (1-40)
• beta-Synuclein
• Vitamin A
• Glutamic Acid

Topics

• Amyloid beta-Peptides (metabolism)
• Animals
• Brain-Derived Neurotrophic Factor (metabolism)
• Dietary Supplements
• Electron Transport (drug effects, physiology)
• Endoplasmic Reticulum (metabolism)
• Glutamic Acid (metabolism)
• Hippocampus (drug effects, metabolism)
• Humans
• Male
• Mitochondria (metabolism)
• Oligopeptides (metabolism)
• Peptide Fragments (metabolism)
• Rats
• Rats, Wistar
• Reactive Nitrogen Species (metabolism)
• Receptor for Advanced Glycation End Products
• Receptors, Dopamine D2 (metabolism)
• Receptors, Immunologic (metabolism)
• Stress, Physiological
• Vitamin A (pharmacology)
• Vitamins (pharmacology)
• alpha-Synuclein (metabolism)
• beta-Synuclein (metabolism)