AsianScientist (Feb. 8, 2018) – Scientists in Japan have identified a molecule that aids a crucial ‘pruning’ process in the brain that, if malfunctioning, could lead to disorders such as autism and dementia. Their findings are published in Neuron.
As the brain develops during the fetal stage and in early life, neurons and their connecting synapses branch out rapidly, like a tree. Over time, these connections become more refined and purposeful via a series of molecular mechanisms that prune the connections. Like a gardener trims a tree, weaker branches are discarded to redirect nutrients to help nurture the stronger branches.
However, genetic and environmental mutations can misguide this process and eliminate far too many synapses or not nearly enough. Either extreme can result in a myriad of neuropsychiatric disorders from autism spectrum disorder to schizophrenia and dementia.
In the present study, a team of scientists led by Professor Masanobu Kano at the University of Tokyo, Japan, have discovered that a molecule called progranulin is a key regulator of brain development and neuronal signaling. Within a typically developing brain, a type of neuron called a Purkinje cell is furnished with climbing fibers. Among multiple climbing fibers innervating each Purkinje cell, a single climbing fiber is strengthened and maintained throughout an animal’s life, whereas the other climbing fibers are weakened and eventually eliminated.
The researchers thus set out to identify a new molecule involved in strengthening and maintaining single climbing fiber inputs. They found that progranulin maintains developing climbing fibers, preventing the fibers from being degraded during the early stages of brain development. They studied a mouse model engineered without progranulin and found that climbing fibers were more quickly eliminated, and climbing fiber input overall was significantly reduced.
“Our results provide a new insights into the roles of progranulin in the developing brain,” said Kano. “We will continue to search for molecules involved in synapse elimination in the developing cerebellum and, ultimately, we want to elucidate entire signaling cascades for synapse elimination.”
Although the researchers do not yet know how to effectively manipulate the molecule, it is possible that progranulin signaling may be a potential therapeutic target for neuropsychiatric disorders.
The article can be found at: Uesaka et al. (2018) Retrograde Signaling from Progranulin to Sort1 Counteracts Synapse Elimination in the Developing Cerebellum.
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Source: University of Tokyo; Photo: Shutterstock.
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