Psych Central News
Mouse Study: Lead Exposure, Genetics Linked to Schizophrenia Risk
The study, published online in Schizophrenia Bulletin, helps scientists better understand the complex gene-environment combinations that result in a greater risk for schizophrenia and other mental disorders.
In 2004, research conducted by scientists at the Columbia University’s Mailman School of Public Health suggested a connection between prenatal lead exposure in humans and increased risk for schizophrenia later in life. And yet, it was still unknown how exposure to lead could trigger the disease.
Based on his own research with rodents, Tomás R. Guilarte, senior author of the new study, believed the answer was in the direct inhibitory effect of lead on the N-methyl-D-aspartate receptor (NMDAR), a synaptic connection point important to brain development, learning and memory.
Guilarte discovered in his research that exposure to lead dulls the function of the NMDAR. The glutamate hypothesis of schizophrenia suggests that a deficit in glutamate neurotransmission—and specifically hypoactivity of the NMDAR — can account for much of the dysfunction in schizophrenia.
In the new study, Guilarte and his team focused on mice engineered to carry the mutant form of Disrupted-in-Schizophrenia-1 (DISC1), a gene that is a risk factor for the disease in humans.
Before birth, half of the mutant DISC1 mice were fed a diet with lead, and half were given a normal diet. Another group, consisting of normal mice without the mutant DISC1 gene, were also split into the two feeding groups. All mice were given a series of behavioral tests, and their brains were examined using MRI.
Mutant mice exposed to lead and given a psychostimulant showed higher levels of hyperactivity and were less able to suppress a startled response to a loud noise after being given an acoustic warning. Their brains also had significantly larger lateral ventricles — empty spaces containing cerebrospinal fluid — compared with other mice. These results reflect what is known about schizophrenia in humans.
Although the role of genes in schizophrenia and other mental disorders is well known, the effects of toxic environmental chemicals is just beginning to emerge.
“We’re just scratching the surface,” said Guilarte. “We used lead in this study, but there are other environmental toxins that disrupt the function of the NMDAR.” One of these is a family of chemicals in air pollution called polycyclic aromatic hydrocarbons or PAHs.
“Similarly, any number of genes could be in play,” added Guilarte, noting that DISC1 is among many involved in schizophrenia.
Future research may reveal to what extent schizophrenia is determined by environmental versus genetic factors or both, and what other mental disorders might be in the mix.
“The animal model provides a way forward to answer important questions about the physiological processes underlying schizophrenia,” said Guilarte.
Source: Columbia University
Schizophrenia word collage photo by shutterstock.
0 comments:
Post a Comment