Researchers at the University of Virginia and the Salk Institute have discovered a molecule, pleiotrophin, whose deficiency may account for incorrect brain wiring in Down syndrome. Pleiotrophin is essential for establishing connections among brain cells. Its reinstatement enhanced brain function in adult mice long after their nervous systems had matured, indicating a novel method for treating Down syndrome. Unlike earlier techniques that required fetal intervention, this approach proved effective post-maturation, creating new possibilities for treatment.
Ashley N. Brandebura, currently at UVA’s School of Medicine, highlighted the importance of focusing on astrocytes to reconfigure brain circuitry in adults as proof-of-concept. Down syndrome, impacting 1 in 640 newborns in the U.S., results from an additional chromosome 21 and leads to intellectual and developmental challenges. The study, spearheaded by Nicola J. Allen at Salk, revealed that the levels of the synapse-building protein pleiotrophin were diminished in mice with Down syndrome.
Primarily produced by astrocytes, pleiotrophin is plentiful during key stages of brain development. Its peak during early postnatal weeks aligns with swift synapse formation. Reintroducing pleiotrophin via virus-modified carriers in 60-day-old mice enhanced neuron complexity and synapse formation, leading to better short-term plasticity in mice with Down syndrome.
Findings indicated that astrocytes can transport plasticity-inducing molecules, hinting at future treatment prospects beyond specific fetal timelines. However, pleiotrophin deficiency is not the only contributor to Down syndrome. Allen’s lab has reported that astrocytes also generate excessive harmful substances. The multifaceted nature of Down syndrome is recognized.
Brandebura mentions broader implications for neurological conditions, including fragile X and Alzheimer’s disease. Diminished pleiotrophin levels were also observed in models of Rett and fragile X syndromes. While clinical application remains a future prospect, and mouse models do not completely mirror human Down syndrome, the idea of reprogramming astrocytes brings promise for tackling various brain circuit disorders.
For further information, consult the published study in Cell Reports.