Researchers at the University of Bonn have revealed how genetic predisposition and environmental factors, such as neuroinflammation, interact to influence neuronal development and contribute to autism spectrum disorders.
Bonn, November 28 – Researchers at the University of Bonn have uncovered new insights into how genetic predisposition and environmental factors converge to shape neuronal development, potentially contributing to autism spectrum disorders (ASD). This work highlights the intricate interplay between genetic risk factors and neuroinflammation in the developing brain and offers a mechanistic explanation for how these elements combine to influence neurodevelopment.
Autism is a complex neurological developmental disorder that impacts social interaction, communication, and perception. While both genetic and environmental contributors are recognized, the precise mechanisms underlying their interaction have remained unclear. The research team, led by Stephan Baader at the Anatomical Institute, focused on Purkinje cells—key neurons in the cerebellum known for their critical role in cerebellar function and structural organization—to investigate these interactions.
The study utilized cerebellar slice cultures to probe the combined effects of genetic overexpression of the autism susceptibility gene Engrailed-2 and inflammatory stimulation using lipopolysaccharide (LPS), an agent known to mimic bacterial infection. Results demonstrated that LPS reduced dendritic growth in Purkinje cells, an effect exacerbated by the overexpression of Engrailed-2. This reduction in dendritic growth could be mitigated by inhibiting microglial proliferation or blocking tumor necrosis factor-alpha (TNF-α) receptor signaling, highlighting the pivotal role of microglia and TNF-α in this process.
The implications of these findings are profound. They suggest that while genetic and environmental risk factors alone may have limited penetrance in causing ASD symptoms, their combination significantly increases the risk. This highlights the importance of considering both genetic susceptibility and environmental exposures, such as prenatal infections, in understanding ASD pathogenesis.
The study, titled “Genetic and environmental risk factors cooperate to affect autistic-like neuronal phenotypes,” was published in the Journal of Neuroinflammation and provides a compelling framework for future research into how these factors interact during critical periods of brain development.
For further information, please refer to the full publication: https://doi.org/10.1186/s12974-024-03301-6
Scientific contact:
Prof. Dr. Stephan Baader
Institute of Anatomy
E-Mail: sbaader@uni-bonn.de
Written by: Dr Michela Barboni, Ph.D
