Toxic dye may cause ALS-like symptoms, neurodegeneration
Exposed zebrafish showed learning and memory deficits, less social activity
Being exposed to rhodamine B (RhB), a toxic fluorescent dye, causes neurodegeneration and symptoms that resemble amyotrophic lateral sclerosis (ALS) in zebrafish, a study reports.
The exposed zebrafish exhibited behaviors, and cellular and molecular changes similar to those in neurological disorders like ALS. Their muscles and motor abilities also changed after exposure.
“Identifying ALS-like behavior in zebrafish, such as neurodegeneration and motor impairment, highlights the potential long-term health implications of environmental exposure to RhB in the brain of zebrafish,” the study’s researchers wrote. Their study, “Rhodamine-B induces Amyotrophic Lateral Sclerosis symptoms like-behaviours in zebrafish,” was published in Aquatic Toxicology.
ALS is caused by the dysfunction and death of nerve cells that help control voluntary movement. As the disease progresses, loss of motor control and other symptoms, such as mood disorders and cognitive problems, may develop.
The risk of developing ALS increases with exposure to certain pesticides and chemicals. Although there isn’t a known association between ALS and RhB, the dye may lead to neurodegeneration and increases oxidative stress, which happens when the body’s antioxidant defenses can’t neutralize unstable molecules called reactive oxygen species.
Results of dye exposure
Manufacturers may illegally use RhB to impart red color on foods, especially in developing countries, meaning “this highly toxic dye poses a major concern for both aquatic and terrestrial ecosystems,” wrote the researchers, who exposed zebrafish, a common model of human neurological disease, to RhB. They chose three test concentrations — 0.25, 0.5, and 1 microM — exposing the zebrafish for three weeks. The researchers also exposed zebrafish to rotenone (RoT), which can induce neurological changes similar to those in ALS and Parkinson’s disease, and also used an unexposed control group.
Significant deficits were shown in learning and memory in the RhB and the RoT groups. The animals also showed aggressive behaviors and significant decreases in social activity.
Another test examined anxiety-like behavior by measuring how zebrafish explore a new environment. Zebrafish typically show initial signs of anxiety and stay close to the bottom of a new tank. Over time, as their anxiety decreases, they begin exploring near the surface. In the exposed fish, “decreased exploratory activity, evidenced by reduced time spent and visits to the top zone of the [new] tank, suggests increased anxiety-like behavior,” the researchers wrote. Exposed zebrafish also spent more time immobile and, when they moved, they moved significantly less than controls.
The researchers examined the zebrafish brains and muscle at the end of the 21-day exposure.
“RhB exposure induced structural changes in the skeletal muscle of zebrafish, characterized by swelling and [tissue death],” they wrote. Signs of neurodegeneration were also found, including irregularly shaped nerve cells.
At the molecular level, groups exposed to RhB saw decreases in levels of neurotransmitters, or chemicals that help nerve cells communicate. Conversely, levels of types of protein that degrades certain neurotransmitters were significantly higher.
Toxin exposures also changed levels of messenger RNA, which indicate changes in how genes are expressed. Several of the impacted genes were involved in neural development and the ability of the nervous system to change in response to changing conditions.
“These findings suggest that RhB exposure can disrupt critical neuronal activities and lead to behavioral changes,” wrote the researchers, who said behavioral, cellular, and molecular changes may be related to how RhB enhances oxidative stress. Among the changes related to oxidative stress in the brain, increased levels of reactive oxygen species and altered activity of enzymes involved in maintaining healthy levels of oxidant molecules were observed.
“Excessive reactive oxygen species production and accumulation damage the structure of cell membranes and the biological functions of lipids (fat-like molecules), proteins, and DNA, ultimately leading to the initiation of neuronal cell damage and the development of neurodegenerative diseases, such as [ALS],” wrote the researchers, who said their study shows exposure to RhB induces significant neurotoxic effects in zebrafish. “These findings suggest that RhB can disrupt critical neuronal processes, leading to neurodegenerative changes.”
About the Author
