Toxins , Genetic Susceptibility and Autism

Toxicity of the Flame-retardant BDE-49 on Brain Mitochondria and Neurons Enhanced by a PTEN-deficient Background.

http://www.ncbi.nlm.nih.gov/pubmed/23288049

Department of Molecular Biosciences, School of Veterinary Medicine.

Abstract

Polybrominated diphenyl ethers (PBDEs) represent an important group of flame-retardants extensively used, which tonnage in the environment has been steadily increasing over the past 25 years.

PBDEs or metabolites can induce neurotoxicity and mitochondrial dysfunction (MD) through a variety of mechanisms. Recently, PBDEs with <5 Br substitutions (i.e., BDE-47 and BDE-49) had gained interest because of their high bioaccumulation. In particular, congeners such as BDE-49 arise as one of the most biologically active with concentrations typically lower than those observed for BDE-47 in biological tissues; however, its potential to cause MD at biologically relevant concentrations is unknown.

To this end, the effect of BDE-49 was studied in brain mitochondria and neuronal progenitor striatal cells (NPC). BDE-49 uncoupled mitochondria at concentrations <0.1 nM, whereas at <1 nM inhibited the electron transport at Complex V (mixed type inhibition; IC50 = 6 nM) and Complex IV (noncompetitive inhibition; IC50 = 40 nM). These concentrations are easily achieved in plasma concentrations considering that BDE-49 (this study, 400-fold) and other PBDEs accumulate 1-3 orders of magnitude in the cells, particularly in mitochondria and microsomes. Similar effects were observed in NPC, and exacerbated with PTEN (negative modulator of the PI3K/Akt pathway) deficiency, background associated with autism-like behavior, schizophrenia and epilepsy. PBDE-mediated MD per se or enhanced by a background that confers susceptibility to this exposure, may have profound implications in the energy balance of brain.

Advertisements
This entry was posted in Autism, Environment, Genetics, Physiology and tagged , , , , , . Bookmark the permalink.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s