New Study finds Sex Differences in Adult Neurogenesis in the Hippocampus

Like many areas of science, neurogenesis is one where little work has been done looking at sex differences. 

Neurogenesis is the process where new neurons are formed in the brain, which happens in the adult hippocampus. Previous research in this area has largely focused on male subjects, which has prevented researchers from understanding how this process might differ in females.

In a new paper, Dr. Liisa Galea (pictured) and Shunya Yagi (pictured below, back left in blue shirt), a PhD Candidate in Neuroscience, found there is in fact a difference in the regulation of neurogenesis in the hippocampus between male and female rats. 

“The majority of studies that use both males and females aren’t actually analyzing by sex, which is very problematic because it means we’re missing out on important distinctions,” says Dr. Liisa Galea, DMCBH researcher and Professor in the Department of Psychology. “As a researcher interested in sex differences, I wasn’t even convinced that we’d see any differences in neurogenesis between males and females and yet we found some significant ones, which goes to show just how essential it is to take sex into consideration.”

The study—which was part one of first author Shunya Yagi’s PhD thesis—looked at two-month-old rats (equivalent to young adults in humans) and compared the trajectory and maturation rate of adult-born neurons over the course of three weeks. This was done by injecting dye into dividing cells and following them over time so see how they changed.  

The team found that while new neurons reached the same level of maturation at the end of a three-week period, males got to this end point much faster. Males also had a different trajectory, with an early and fast uptake, followed by a rapid decline in new neurons. Females, on the other hand, had a more “slow and steady” approach to neurogenesis. (pictured: the Galea Lab team bonding).

Another interesting finding is that there were more new neural stem cells found in the dorsal region of the hippocampus in males, which is important for learning and memory. Neural stem cells are capable of churning out new brain cells which means they have the potential of generating new neurons. Females had far fewer neural stem cells in this area; instead, these neural stem cells in females were more concentrated in the ventral region of the hippocampus which plays an important role in stress.

“Of course, even though males have more new neurons in the dorsal region than females, females can still learn—but it’s interesting to think about why there might be a difference between the two sexes and what impact this has,” says Dr. Galea. “This could have important implications for brain disorders that have disrupted neurogenesis and show sex differences when it comes to symptoms. Alzheimer’s is a good example, where females are disproportionately affected and show faster and steeper cognitive decline with the disease.”

This study highlights the importance of studying biological sex differences in neuroscience and provides insight into the ways in which males and females differ when it comes to neurogenesis. This research endeavour was also somewhat of a family affair, with Dr. Galea’s son Jared Splinter (pictured: back left with sunglasses) in UBC’s Physics and Astronomy Department taking part by writing the code used to count the neural stem cell population.

This work is ongoing, and the next steps will involve looking at patterns of activation of new neurons to memory to determine whether these neurons in males and females are equally active, or if there’s a disparity in one sex. The team will also be studying the consequences—if any—that these differing trajectories and maturation rates might have for male versus female rats.