Mechanism of action of l-theanine on cerebellar granule cell migration via signaling pathways.

l-theanine is derived from green tea leaves. It has neuroprotective properties that promote brain development through the migration of cerebellar granule cells, but its exact mechanisms remain unclear. In this study, we examine receptor-mediated CGC migration signaling pathways modulated by l-theanine. We treated cerebellar explants and primary CGCs from postnatal mice with l-theanine (0.1-1000 µm), with and without receptor blockers CNQX, MK-801, and bicuculline. Changes at the cellular level and activation of signaling proteins were studied. The results showed that l-theanine stimulated CGC migration in a dose- and time-dependent manner. This stimulatory effect was nullified by blocking the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartic acid receptors and was enhanced by blocking GABAA receptors. Moreover, l-theanine stimulated the phosphorylation of ERK1/2, calmodulin kinase II, CREB, and AMPA, indicating activation of pathways related to synaptic plasticity and cytoskeletal changes. These findings suggest that l-theanine likely promotes CGC migration through specific receptor pathways, supporting its role in neurogenesis.