New evidence suggests the factors that contribute to learning problems associated with an inherited brain tumor disorder are much more complex than expected.
Researchers at Washington University School of Medicine in St. Louis discovered the learning and attention problems associated with neurofibromatosis 1 (NF1), are multifactorial.
NF1 is among the most common inherited pediatric brain cancer syndromes with children frequently developing low-grade brain tumors.
“While one of our top priorities is halting tumor growth, it’s also important to ensure that these children don’t have the added challenges of living with learning and behavioral problems,” says senior author David H. Gutmann, M.D., Ph.D.
“Our results suggest that learning problems in these patients can be caused by more than one factor. Successful treatment depends on identifying the biological reasons underlying the problems seen in individual patients with NF1.”
The study appears online in Annals of Neurology.
According to Gutmann, scientists are divided when considering the basis for NF1-associated learning abnormalities and attention deficits.
Mutations in the Nf1 gene can disrupt normal regulation of an important protein called RAS in the hippocampus, a brain region critical for learning. Initial work from other investigators had shown that increased RAS activity due to defective Nf1 gene function impairs memory and attention in some Nf1 mouse models.
However, earlier studies showed that a mutation in the Nf1 gene lowers levels of dopamine, a neurotransmitter involved in attention.
The new research suggests that both sides may be right.
In the latest study, postdoctoral fellow Kelly Diggs-Andrews, Ph.D., found that the branches of dopamine-producing nerve cells that normally extend into the hippocampus are shorter in Nf1 mice. As a result, dopamine levels are lower in that part of the brain.
“These results and the earlier findings suggest that there are a variety of ways that NF1 may cause cognitive dysfunction in people,” Gutmann says.
“Some may have problems caused only by increased RAS function, others may be having problems attributable to reduced dopamine, and a third group may be having difficulties caused by both RAS and dopamine abnormalities.”
To customize patient therapy, Gutmann and his colleagues are now working to develop ways to quantify the contributions of dopamine and RAS to NF1-related learning disorders.