Researchers have identified potential treatment targets for preventing autism development in newborns. Photo by ramosiquitios/Pixabay
Feb. 21 (UPI) — Blocking an overactive signaling pathway in the brain during the first five weeks of life prevents mice from developing autism symptoms, a study published Monday by the journal JNeurosci found.
Mice treated with the drug rapamycin early in life did not develop symptoms, the data showed.
The drug, an antibiotic that has been sold under the brand name Sirolimus, among others, works by blocking mTOR signaling, a pathway in the brain and central nervous system involved in cell growth and development, the researchers said.
Abnormal signaling in this pathway has been found in people and animals with tuberous sclerosis complex, a neurodevelopmental disorder closely linked with autism spectrum disorder, they said.
Treatment administered during critical periods of child development could prevent autism symptoms from ever manifesting, researchers from UT Southwestern Medical Center in Dallas said.
Because tuberous sclerosis complex often is diagnosed in humans, defining these critical periods may provide an opportunity to prevent development of autism behaviors, the researchers said.
After four weeks of treatment, starting at one week of life, mice displayed normal social behaviors and normal brain cell activity — even after four weeks without treatment, according to the researchers.
Earlier research by this same team identified periods of early life during which treatment with rapamycin could help prevent the development of autism spectrum disorder, a developmental disorder that causes problems with social interaction and communication.
The disorder affects one in 44 children born in the United States, according to Autism Speaks.
In a separate study published last week by the journal Genome Biology, researchers identified a genetic mutation in the placentas of newborns later diagnosed with autism.
Their research also connected the mutated gene with maternal early prenatal vitamin use and placental oxygen levels, suggesting that steps taken early in fetal or newborn development could help prevent the disorder, they said.
The placenta supports fetal development in the uterus by regulating oxygen supply and metabolism and providing critical hormones and brain cells. During pregnancy, the fetus may experience oxidative stress, an imbalance of free radicals and antioxidants in the body that is common in normal brain development.
However, in some cases, exposure to environmental factors such as air pollution and pesticides can lead to excessive oxidative stress, which can lead to cell and tissue damage or delayed development, the researchers said.
They studied the development of 204 children born to mothers who had at least one older child with autism and were considered at higher risk for having another child with the disorder.
When these children were born, the mothers’ placentas were collected and preserved for future analysis, said the researchers, who extracted and quantified the DNA from the placenta tissue.
These children were then assessed for the disorder at age 3. In their analysis of placenta tissue, the researchers identified mutations in a region of chromosome 22 not previously linked with autism, they said.
They also spotted a new gene in the region called LOC105373085, which they renamed NHIP, or neuronal hypoxia inducible, placenta associated.
In subsequent experiments, they found that NHIP is activated in neurons after hypoxia, a state of low oxygen levels, and regulates other gene pathways with functions in brain development and response to oxidative stress, they said.
“We found that the NHIP gene is active in the brain, responsive to oxidative stress, and influences expression of other known genes associated with autism,” study co-author Janine LaSalle said in a press release.
“In most pregnancies, the placenta experiences some inevitable levels of stress, [and] we think that NHIP is there to buffer the effects of excessive oxidative stress,” said LaSalle, a professor of microbiology and immunology at UC Davis Health in California.
This is important because in the placenta, hypoxia triggers placental cell division to make further contact with maternal blood vessels to supply enough oxygen for the developing brain, she said.
Conversely, NHIP was less activated in the placentas and brains of children later diagnosed with autism, which means the gene may help prevent the disorder from developing, she and her colleagues said.
The use of prenatal vitamins, which are high in folic acid and can reduce oxidative stress, during the first month of pregnancy showed a significant protective effect among individuals with genetic differences in NHIP region, the researchers said.
As a result, taking prenatal vitamins in the first month of pregnancy seems to provide essential metabolic elements to counteract the genetic inheritance of differences that may lead to autism development, they said.
“We found that taking a prenatal vitamin is essential when planning a pregnancy,” LaSalle said.
“Findings from our study provide key insights that may help in identifying newborns more likely to develop autism and getting them into an earlier intervention or just knowing to watch them sooner,” she said.