According to Marshall University Joan C. Edwards School of Medicine experts, brain cells may find distinct methods to connect with each other during development based on sex.
When exposed to factors secreted by astrocytes, which are non-neuronal cells found throughout the central nervous system, male-derived cells showed a significantly more robust synaptogenic response than female-derived cells, according to the study, which was recently published in eNeuro, an open-access journal for the Society of Neuroscience.
The response of neurons to thrombospondin-2 (TSP2), a cell adhesion protein ordinarily released by astrocytes, was a major factor in this discrepancy. TSP2 caused a significant increase in synapses in male neurons in the study but had no effect on female neurons.
This research shows that synapses, which are the fundamental building blocks of brain connectivity, can be generated by a variety of methods during early development.
“Our goal is to better understand at a basic cellular level if there are sex differences in how cellular networks form in the brain,” said W. Christopher Risher, Ph.D., an assistant professor of biomedical sciences at the Joan C. Edwards School of Medicine and corresponding author on the study.
“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.”
Our goal is to better understand at a basic cellular level if there are sex differences in how cellular networks form in the brain. 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.
W. Christopher Risher
For this work, Risher’s team separated brain cells (neurons and astrocytes) from male and female newborn rats, lead by first author Anna Mazur, Ph.D. After the cells were extracted, they were cultivated for up to two weeks in various combinations with one another, and the number of synapses established was counted using a fluorescent microscope at the end of the experiment.
In addition, the cells were treated with TSP2 and a variety of estrogen signaling regulators to see how each of these factors affected synapse development in male and female-derived cultures.
“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,” Risher said.
Risher and his colleagues are still investigating the presence and consequences of inequalities in cellular networks. Finally, the findings from their research could open the door for sex-specific therapy for neurodevelopmental illnesses with strong sex biases in humans, such as autism spectrum disorder and schizophrenia.
