Despite 50 years of efforts to reduce lead exposure, the situation continues to be a significant public health problem for many Americans. More than 250,000 children in the U.S. show elevated levels of lead in their blood, and the annual costs for poisoning exceeds $43 billion. Sadly, the issue balloons on an international scale.
[Photo: Dean Tomás R. Guilarte]
As principal investigator of a study funded by the National Institute of Environmental Health Sciences (NIEHS), Dr. Tomás R. Guilarte, dean of Florida International University’s (FIU) Robert Stempel College of Public Health and Social Work, has discovered a potential therapy that could reverse the heavy metal’s harmful effects in children.
Lead poisoning disrupts synaptic processes by blocking the chemical signals sent between neurons, which connect to one another through a tiny gap called a synapse. Brain-derived neurotrophic factor (BDNF) is necessary to promote the survival of these synapses and requires calcium to work. Lead inhibits N-methyl-D-aspartate (NMDA) receptor mediated calcium entry into neurons restricting the production of BDNF and weakening the synapses over time.
The new research demonstrates that activation of TrkB receptors, the cognate receptor for BDNF by 7,8-Dihydroxyflavone (7,8-DHF), can reverse the long-term effects of lead exposure on neurotransmitter release in synapses. For more information, see “7,8-Dihydroxyflavone Rescues Lead-Induced Impairment of Vesicular Release: A Novel Therapeutic Approach for Lead Intoxicated Children” which was published in the October 2017 issue of Toxicological Sciences, the official journal of the Society of Toxicology.
This blockage is extremely detrimental to children because their brains are in a nonstop process of growth and development. Learning disabilities and behavioral problems are all possible consequences of synaptic dysfunction induced by lead.
The naturally-derived and safe 7,8-DHF molecule is able to cross the blood-brain barrier and establish a complete reversal of lead-induced impairments of synaptic dysfunction; Dr. Guilarte believes this is a beacon of hope for developing novel approaches for a permanent reversal of damage.
The next step for Dr. Guilarte’s research team is to demonstrate that 7,8-DHF also improves learning performance in the same animal model. Then, they will conduct a translational study from animals to humans.