US researchers discover sex differences in development of brain cell networks

20th July 2021 By: Rebecca Campbell - Creamer Media Senior Deputy Editor

Researchers at the Joan C Edwards School of Medicine at Marshall University (in Huntington in the US state of West Virginia) have discovered evidence that there are differences in the development of neuron (brain cell) networks between males and females in mammals. Their research has shown that the synaptogenic response in brain cells derived from new-born male rats is substantially more robust that that in cells derived from new-born female rats, when these cells were exposed to elements secreted by cells called astrocytes. Astrocytes are non-neuronal cells that are scattered throughout the central nervous system.

Synapses form the basic elements for brain connectivity. The study showed that male- and female-derived neurons responded differently when exposed to a protein normally secreted by astrocytes, called thrombospondin-2 (TSP2). In the male-derived cells, the TSP2 prompted strong increases in synapse development, but in the female-derived cells, it had no effect.

“Our goal is to better understand at a basic cellular level if there are sex differences in how cellular networks form in the brain,” explained study corresponding author and Joan C Edwards School of Medicine assistant biomedical sciences Professor W Christopher Risher. “In this study, for the first time, we see evidence that events which were always assumed to be occurring in the same manner, regardless of sex, may actually be completely different in males compared to females. The fact that these differences involve astrocytes, which have traditionally been ignored in neuroscience but have recently become a hot topic for study, makes them all the more intriguing.”

The research team is headed by study lead author Dr Anna Mazur. Its other members are Ean Bills, Kayla DeSchepper, James Willimson and Brandon Henderson. The team is continuing its research into the existence and effects of differences in cellular networks.

“The fact that we have identified molecular pathways present in males that are either absent or less prominent in females indicates that there may be much that researchers have missed in the area of synaptic development, simply because we weren’t looking separately at males and females,” highlighted Risher. This and further research by the team could ultimately lead to the development of sex-specific treatments for neurodevelopmental disorders. Such disorders include the autism spectrum and schizophrenia, which appear in humans with strong sex biases.