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Astrocytes regulate the formation of synapses in neurodevelopment.

During brain development, the formation of neuronal synapses at the right time, the right place, and the right strength are crucial to the ongoing function of the brain throughout life. However, just how this happens, and the molecular signals involved are still not fully understand. Now, a study from researchers at the Salk Institute shows brain cells called astrocytes initiate communication between a set of neurons early in neurodevelopment by inducing specific changes in both members of the pair. The team states their work has important implications for neurodevelopmental disorders such as autism, ADHD, and schizophrenia, conditions caused at least partly from faulty communication between neurons. The opensource study is published in the journal Neuron.

Previous studies show astrocytes are necessary for neurons to form synapses, with recent studies from the lab showing a protein secreted by astrocytes named glypican 4 induced communication between neurons. With glypican 4 present, presynaptic neurons sending information partner effectively with the postsynaptic neurons receiving them. However, the exact mechanism behind this process is unknown. The current study investigates the molecular mechanisms involved in glypican 4 exerting its effect.

The current study treats cultures of neurons with either glypican 4 or another astrocyte-secreted protein called thrombospondin, inducing changes in neurons. Results show forty-nine genes are activated in response to treatment with glypican 4, with three genes activated in response to thrombospondin. The lab explains the fact there is no overlap between the genes suggests the two proteins are involved in very different cellular systems, with glypican 4 critical for making synapses active, and thrombospondin ensuring the synapses remain stable.

Results show glypican 4 increases the number of receptors receiving postsynaptic neurons. Data findings show glypican 4 recruits receptors to the cell surface by inducing the release of a protein called neuronal pentraxin 1 (NP1) that directly binds to the receptors. The group states without NP1 binding to the receptors synapses remain silent meaning glypican 4 is needed to make postsynaptic neurons receptive to input. They conclude presynaptic neurons release NP1 specifically in response to glypican 4, suggesting a single protein released by astrocytes is responsible for enabling connections between neurons.

The team surmises their data identifies a signaling pathway that regulates synaptic activity during neurodevelopment.  For the future, the researchers state their work will explore ways of targeting astrocytes and synaptic regulation to develop novel therapies for neurological disorders.

Source: Salk Institute for Biological Studies

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