Neural stem cells (green) migrate throughout an injured brain site in DLB mice and begin to differentiate into astrocytes (red), leading to improved motor and cognitive function. Blurton-Jones lab
DLB is the 2nd-most common type of age-related dementia after Alzheimer’s disease and is characterized by the accumulation of a protein alpha-synuclein that collects into spherical Lewy bodies – which also accumulate in related disorders, including Parkinson’s disease. This pathology, in turn, impairs the normal function of neurons, leading to alterations in critical brain chemicals and neuronal communication and, eventually, to cell death.
One day transplantation of neural stem cells into human patients might help overcome the motor and cognitive impairments of DLB. To test this idea, they transplanted mouse neural stem cells into genetically modified mice exhibiting many of the key features of DLB. One month later, the mice were retested on a variety of behavioral tasks, and significant gains in both motor and cognitive function were observed. For example, these mice could run on a rotating rod for much longer and recognize novel objects far better than untreated DLB mice.
MOA: Goldberg and colleagues examined the effects of the stem cells on brain pathology and circuitry connecting neurons. They found that functional improvements required the production of a specific growth factor – called brain-derived neurotrophic factor – by neural stem cells.
2 key brain structures become dysfunctional in DLB – dopamine- and glutamate-making neurons – to determine how BDNF might drive recovery. “…neural stem cells can enhance the function of both dopamine-and glutamate-producing neurons, coaxing the brain cells to connect and communicate more appropriately. This, in turn, facilitates the recovery of both motor and cognitive function,” Goldberg said.
Testing the possibility that BDNF alone might be an effective treatment, Goldberg used a virus to deliver the growth factor to the brains of DLB mice. This resulted in good recovery of motor skills in the test rodents but only limited recovery of cognitive function. This, Goldberg said, suggests that while BDNF is critical to stem cell-mediated motor and cognitive recovery, it does not achieve this outcome alone. These results imply that transplantation of BDNF-producing neural stem cells may one day offer a new approach for treating DLB.
“Many important questions remain before we could envision moving forward with early-stage trials,” Blurton-Jones said. “For example, we’ll need to identify and test human neural stem cells first.”
BDNF-producing neural stem cells might also be beneficial for several other diseases. “BDNF, dopamine and glutamate are implicated in other neurodegenerative conditions, including Huntington’s and Alzheimer’s disease,” Goldberg noted. http://news.uci.edu/research/stem-cell-treatment-lessens-impairments-caused-by-dementia-with-lewy-bodies/
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