A team of scientists led by researchers at the University of
Georgia has developed a new mouse model that closely mimics fetal brain
abnormalities caused by the Zika virus in humans.
This model, described in a paper published recently in the
journal Development, may help scientists better understand how the Zika virus
affects different cell types in the developing brain, which could hasten the
creation of new treatments and diagnostics…
"A lot of the discussion about Zika has focused on
microcephaly, and while that is certainly important, we found that the virus
causes additional devastating damages to the developing brain as well,"
said Jianfu "Jeff" Chen, an assistant professor of genetics in UGA's
Franklin College of Arts and Sciences.
Most notably, Chen and his colleagues, including
postdoctoral fellow Qiang Shao and graduate student Stephanie Herrlinger, found
that Zika infection leads to abnormal blood vessel formation in the brain and a
leaky blood-brain barrier, which normally protects the brain from potentially
harmful pathogens.
"In addition to neural progenitor cell disruption,
which is a classical cause of human microcephaly, we also observed massive
death of neuronal cells in our mouse model," Chen said. "This
combined with the disruption of the vascular system and the blood-brain barrier
results in microcephaly and extensive brain damage."
Therefore, he added, "It's not just that the brain is
smaller than normal; it is severely injured as a result of the infection, and
we need to understand all these effects if we are going to develop successful
therapies."
The researchers created their model by injecting Zika virus
that was isolated in Mexico from an infected mosquito into the brain of mouse
embryos. They were then able to observe the neurological effects after the mice
were born.
"A lot of scientists are looking for postnatal mouse
models to study the effects of Zika virus infection, but the virus often causes
premature birth in mice," Chen said. "The virus-infected pups in our
model were carried to term, and they were born alive. This is important,
because some infected babies were also born alive in humans, and establishing a
postnatal mouse model will be a good start to understand potential neurological
complications after virus infection."
Qiang Shao, Stephanie Herrlinger, Si-Lu Yang, Fan Lai, Julie
M. Moore, Melinda A. Brindley, Jian-Fu Chen. Zika virus infection disrupts
neurovascular development and results in postnatal microcephaly with brain
damage. Development 2016 : doi:
10.1242/dev.143768
Abstract
Zika virus (ZIKV) infection of pregnant women can result in
fetal brain abnormalities. It has been established that ZIKV disrupts neural
progenitor cells (NPCs) and leads to embryonic microcephaly. However, the fate
of other cell types in the developing brain and their contributions to
ZIKV-associated brain abnormalities remain largely unknown. Using intracerebral
inoculation of embryonic mouse brains, we found that ZIKV infection leads to
postnatal growth restriction including microcephaly. In addition to cell cycle
arrest and apoptosis of NPCs, ZIKV infection causes massive neuronal death and
axonal rarefaction which phenocopy fetal brain abnormalities in humans.
Importantly, ZIKV infection leads to abnormal vascular density and diameter in
the developing brain, resulting in a leaky blood-brain-barrier (BBB). Massive
neuronal death and BBB leakage indicate brain damage, which is further
supported by extensive microglial activation and astrogliosis in virally
infected brains. Global gene analyses reveal dysregulation of genes associated
with immune responses in virus-infected brains. Thus, our data suggest that
ZIKV triggers a strong immune response and disrupts neurovascular development,
resulting in postnatal microcephaly with extensive brain damage.
Courtesy of: https://www.mdlinx.com/neurology/medical-news-article/2016/11/23/zika-infection-postnatal-brain-damage/6945252/?category=latest&page_id=3
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