BRF newsletter 062124 pages (1) - Flipbook - Page 5
New Discoveries in Real Time
a powerful tool in visualizing the processes that were
previously only hypothesesiii. “I’ve been able to try this new
way of looking at things that lets us look at it in real time, in
a way that we couldn’t before.”
BRF’s Seed Grant Program was crucial for fueling the
lab’s transition to zebra昀椀sh, allowing their transparent
brains to show a real-time view of neurological cell
relationships and interactions. This unique and
revolutionary form of visualization will no doubt set a
new standard for brain research and make space for
the 昀椀eld to 昀氀ourish even further.
8-day-old zebra昀椀sh larvae expressing di昀昀erent 昀氀uorescent
markers for cells activating an antiviral immune response (green)
and myeloid cells (red) including macrophages and microglia in
the brain. The 昀椀sh is also expressing 昀氀uorescent labels for the
heart and lens.
Applying These Findings to
Brain Disease
Children’s brains are often referred to as being like sponges.
As Dr. Molofsky explained, that’s because most synapse
formation is happening in early childhood, with the peak
being between one and two years of age. After that, there
is a reduction in the number of synapses in the brain. As
humans grow, the strong synapses are preserved and the
weak ones are taken away, as the adult brain becomes more
de昀椀ned, and the focus becomes on speci昀椀c learning.
i
Microglia are essential for this housekeeping activity
within the brain, and as immune cells they harness
signals from the immune system to do it. However, Dr.
Molofsky described the 昀氀ip side of this. “It does raise the
question of what happens if we have too much of a good
thing, right?” There is a hypothesis that some mental
illnesses, such as schizophrenia, may be due to too much
synapse elimination. Alternatively, viral illnesses may spur
overactivity that could contribute to certain diseases.
“What happens if the virus drives that immune response
into overdrive? Do we get microglia ge琀琀ing rid of parts
of the brain that we need?” Focusing on the immune
cells of the brain may help chart the course for a be琀琀er
understanding of other diseases of brain development
such as autism spectrum disorder, epilepsy, and
schizophrenia, as mentioned above.
Alzheimer’s, a common neurodegenerative disease
a昀昀ecting many of our elderly loved ones, could be another
disease that is be琀琀er understood through continued
research on microglia. “Many of the top risk genes in
Alzheimer’s disease are expressed in microglia. So,
microglia have become a huge focus of understanding
Alzheimer’s.” As scientists continue to work on
understanding the factors involved in these diseases,
donor-funded programs such as those o昀昀ered by BRF
provide them with more resources to do so.
The Potential of Donor-Funded
Research
Dr. Molofsky and her team continue to further their
research in the hopes of bringing even more clarity to
the relationship between microglia and brain disease.
BRF grants allow scientists the opportunity to expand
into new arenas of research, enabling them to ask pivotal
questions and gain valuable answers. “We really wanted
to follow the science and be able to take that risk,” Dr.
Molofsky concluded. Investigating in science leads to
new methodologies, new understandings, and newfound
hope for any potential prevention and treatment for these
diseases that alter the lives of so many.
Colonna M, Butovsky O. Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annu Rev Immunol.
2017 Apr 26;35:441-468. doi: 10.1146/annurev-immunol-051116-052358. Epub 2017 Feb 9. PMID: 28226226; PMCID: PMC8167938
ii
iii
Nguyen, Phi T et al. “Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity.” Cell vol. 182,2 (2020): 388-403.e15.
doi:10.1016/j.cell.2020.05.050
Escoubas, Caroline C et al. “Type-I-interferon-responsive microglia shape cortical development and behavior.” Cell, S00928674(24)00186-7. 8 Mar. 2024, doi:10.1016/j.cell.2024.02.020