Intermittent theta burst stimulation (iTBS) is increasingly explored as a non-invasive neuromodulatory approach capable of inducing long-lasting plasticity with potential therapeutic value in age-rela Show more
Intermittent theta burst stimulation (iTBS) is increasingly explored as a non-invasive neuromodulatory approach capable of inducing long-lasting plasticity with potential therapeutic value in age-related neurological and psychiatric conditions. However, the cellular and molecular mechanisms underlying iTBS protocols remain largely unknown, limiting its further therapeutic development. Here, we investigated the behavioral, structural, synaptic, and calcium-dependent effects of a 7-day iTBS600 protocol using a combination of Prolonged iTBS did not alter general locomotor activity, anxiety-like behavior, or short-term recognition memory, indicating preserved baseline behavioral function. Despite the absence of behavioral changes, prolonged iTBS induced robust structural plasticity in hippocampal CA1 neurons, increasing total spine density and selectively enhancing the proportion of thin, learning spines. Synaptosomal analysis revealed upregulation of GluN1 and GluN2A, elevated BDNF levels, and activation of downstream Akt, ERK1/2, and mTOR pathways. Prolonged iTBS also enhanced perineuronal net formation around PV Together, these findings indicate that prolonged iTBS drives coordinated structural, synaptic, and Ca Show less
Batten disease is characterized by early-onset blindness, juvenile dementia and death within the second decade of life. The most common genetic cause are mutations in CLN3, encoding a lysosomal protei Show more
Batten disease is characterized by early-onset blindness, juvenile dementia and death within the second decade of life. The most common genetic cause are mutations in CLN3, encoding a lysosomal protein. Currently, no therapies targeting disease progression are available, largely because its molecular mechanisms remain poorly understood. To understand how CLN3 loss affects cellular signaling, we generated human CLN3 knock-out cells (CLN3-KO) and performed RNA-seq analysis. Our multi-dimensional analysis reveals the transcriptional regulator YAP1 as a key factor in remodeling the transcriptome in CLN3-KO cells. YAP1-mediated pro-apoptotic signaling is also increased as a consequence of CLN3 functional loss in retinal pigment epithelia cells, and in the hippocampus and thalamus of Cln3 Show less
Batten disease is characterized by early-onset blindness, juvenile dementia and death during the second decade of life. The most common genetic causes are mutations in the