PCBs alter key brain chemical that stops nerve-to-nerve signals.
March 14th 2010 21:12
Signature Tune
New cell research fine tunes our understanding of how PCBs affect brain function the compounds enhance the signal of an important brain chemical that normally squelches nerve messages.
Certain types of PCBs can affect the way a brain chemical responsible for halting brain signals sends its chemical messages from nerve to nerve, according to research conducted on frog egg cells. These results further tease apart PCBs' complex effects on brain chemicals and better explain how these interactions can result in abnormal brain function.
PCBs are known to affect behavior, memory and learning in animals and people. Exactly how they do this still eludes researchers, although the persistent contaminants have been shown to affect several key cell chemical pathways that are essential for normal brain activity. Prior studies have focused on how PCBs interfere with the brain chemicals that allow the brain's nerve cells called neurons to communicate.
Yet, little is known about how PCBs impact the opposing yet equally important chemical signals that inhibit and stop nerve messages from crossing the gaps or synapses between nerve endings. This study from the Netherlands finds that some types of PCBs can affect the main inhibitory neurochemical GABA. Signals that suppress chemical messages play just as important a role in producing behavior, memory and learning as does stimulatory signaling.
PCBs are industrial chemicals historically used as insulators and coolants in electrical applications. They persist in the environment and can accumulate in fatty tissues of people and animals. Because of these properties, their use is now banned in most industrialized nations.
People are typically exposed to mixtures of different PCBs through food or by inhaling them in contaminated buildings. Exposure is especially a concern when PCBs are passed from a mother to a fetus in her womb or to her nursing infant, since the developing brain is most sensitive to their effects.
All PCBs have the same chemical backbone structure with a variable number of chlorine atoms attached to it. Where these chlorine atoms sit on the backbone distinguishes the PCB type. Some PCBs can act similar to dioxin, a cancer-causing chemical. However other PCBs do not act like dioxin. These types seem to cause more of the effects on the nervous system.
The most common way that neurons communicate in the brain is by sending a neurochemical (such as serotonin or GABA) from one neuron (the pre-synaptic neuron) across the synapse to the next neuron (the post-synaptic neuron). There, the neurochemical binds a receptor molecule that transmits the signal to cells. Most PCB research has focused on changes in the pre-synaptic neuron.
Not so in this study. The authors used a common method to study the effects of PCBs on human post-synaptic neurons. They injected a copy of the DNA for the human GABA receptor into eggs from African clawed frogs and treated them with mixtures of GABA and different PCBs. This allowed them to study the effects of select PCBs on the human GABA receptor.
They found that some types of PCBs but only in the presence of small amounts of GABA enhanced GABA's ability to inhibit signals by increasing the normal electrical current that GABA generates when it binds to its receptor. Effects were seen only with simpler PCBs that have a small number of chlorine atoms 3 or 4 rather than the maximum of 10 and in those PCBs that do not act like dioxin.
The interactions, though, can be very complex. PCB 153 a non-dioxin-like PCB with 6 chlorine atoms dampened the effects of the simpler PCBs.
The levels of PCBs needed to produce an effect were higher than those that would typically be found in the brain of someone exposed to PCBs. However, the authors point out that if the effects of different PCBs can add up, then the sum of the PCB concentrations that cause the effect in the study could be in the range encountered in humans exposed to PCBs.
Also, these results show the types of effects on GABA signaling from a short-term or acute exposure. Yet PCB exposure typically is long-term. The nervous system can react to changes, so long-term exposures may produce different effects from short-term exposures.
Despite these caveats, the strong point of this study is that it is able to provide important insight into the vexing question of how PCBs affect chemical signaling in the brain.
| 37 |
| Vote |
Add To: 
subscribe to this blog
