A team of researchers has identified a molecular hub in neuronal projections that shapes the plasticity of synapses, according to a new study. Their preclinical work sheds light on the spatial regulation of synaptic plasticity, and hints that the loss of these hubs might play a role in Alzheimer’s disease. Synaptic plasticity in neurons enables learning, but it requires changes in the expression and location of both RNA and proteins in response to neuronal activity. Many of these changes occur in the soma – the central cell body – while others occur at the synapse, together enabling both rapid and durable changes. Now, Kaushik Chanda and colleagues have found a critical hub in the dendrites – signal-receptive projections branching off the soma – that mediates synaptic plasticity in response to excitatory neurotransmission. The authors performed a comparative analysis of gene expression changes in response to signals associated with long-term potentiation (LTP, strengthening) or long-term depression (LTD, weakening) of synapses. In response to induction of LTP, but not LTD, they found that the long noncoding RNA Gas5 acted as a sort of “glue” for a large ribonucleoprotein complex in the dendrites. Gas5 interacted with various proteins and RNAs that regulate synaptic plasticity and neuronal survival. For example, it interacted with both a microRNA (miRNA) and several of the RNAs that it regulates, sequestering the miRNA and protecting the RNAs from degradation. In response to the activation of neurons linked to LTP, these complexes on Gas5 change. This dynamic was critical for effective LTP and excitatory neurotransmission, as well as spine growth and dendritic branching in neurons in the hippocampus. Furthermore, Gas5 abundance in the brain was decreased in a mouse model of Alzheimer’s disease, suggesting that loss of these dendritic complexes may contribute to the progressive cognitive impairment seen with the condition.

Researchers at the Case Western Reserve School of Medicine have found that semaglutide, a popular diabetes and weight-loss drug, may lower the risk of dementia in people with type 2 diabetes (T2D). The study, published today in the Journal of Alzheimer’s Disease (DOI 10.1177/13872877251351329), suggests T2D patients taking semaglutide had a significantly lower risk of developing dementia compared to other antidiabetic medications. These results were more profound in women and older adults.